Systems and methods for treating tissue with deployable electrode arrays

Abstract

The invention relates to a system and method for treating tissue with a deployable electrode array. Devices, systems, and methods for providing controlled delivery of energy treatment to a tissue site are disclosed. The systems, devices, and methods may include medical device designs having features for holding a flexible substrate having an electrode array in position against an expandable member during delivery to, treatment, and retraction from a tissue site. The medical device also includes features for holding the flexible substrate in a compact stowed configuration during delivery and for retracting the flexible substrate after deployment to facilitate retraction of the medical device after completion of the treatment.

Description

Technical Field

[0001] The present disclosure relates generally to the field of tissue treatment. In particular, the present disclosure relates to devices and methods for use with a flexible substrate having one or more electrodes designed to ablate cells to treat target tissue. Background Art

[0002] Tissue in the body can be treated using excision and removal during a surgical or medical procedure. While such procedures may be necessary to treat more extensive injuries or address various medical conditions, minimally invasive procedures may be used as an alternative in some cases. Where applicable, such procedures may be preferred over more invasive surgical procedures to reduce overall patient risk, damage to surrounding tissue, recovery time, discomfort, and potential harmful side effects. In minimally invasive tissue ablation, target tissue can be treated within the body (e.g., in situ) using procedures that do not involve excision or that may require minimal excision. Some examples of minimally invasive tissue ablation techniques include electrolytic ablation, cryosurgery, chemical ablation (e.g., alcohol injection), thermal ablation (e.g., radiofrequency, microwave), and hydrothermal ablation. The main purpose of these ablation procedures is to destroy abnormal tissue in the target area and promote the regrowth of healthy tissue.

[0003] Another minimally invasive treatment technique involves electroporating the target tissue by locally applying an electric field to increase the permeability of the cell membrane, which can then allow drugs or other chemicals to be introduced into the cells for treatment, or can be used for ablation via a process called irreversible electroporation. Electroporation can also be used in combination with electrolysis as a method of tissue ablation through a process also known as electrolytic electroporation, electroporation-electrolysis, or E2.

[0004] Tissue ablation is a therapeutic procedure for treating damage to various tissues (such as tissues of the gastrointestinal tract, lungs, heart, uterus, endometrial lining, ovaries, ureters, prostate, skin, muscles, and other tissues). Tissue ablation has the potential to be a minimally invasive therapeutic procedure for targeted treatment of cancer and other ablation applications. As an example, damage to intestinal tissue may come from a variety of sources, but is generally associated with chronic metabolic diseases (such as diabetes). For diabetic patients, damage to gastrointestinal tissue (particularly the duodenum) may produce problems with insulin resistance and / or impair the body's ability to process glucose. In order to help improve patient management of the disease, duodenal mucosal resurfacing or regeneration (DMR) has been proposed to resurface the patient's intestinal lining and help regenerate a healthy lining to improve nutrient absorption at the duodenum. The improved health of the intestinal lining helps to correct absorption problems and can produce a better therapeutic response to insulin for patients, which in turn can allow some patients to replace more aggressive insulin therapy (e.g., injection) with oral medication to help manage the disease.

[0005] Typically, DMR is a procedure that involves introducing a catheter (or other suitable medical device) into the duodenum, usually under endoscopic guidance, and ablating the inner lining of the duodenum. However, various ablation techniques and ablation device designs may not be suitable for intraluminal ablation, or may be difficult to control ablation to a desired depth via application from within the duodenal lumen.

[0006] The inventors have recognized the need for an improved medical device for use with a flexible substrate having one or more electrodes to ablate cells in order to treat target tissue. Some aspects of the improved medical device include a flexible substrate designed to minimize trauma to surrounding tissue during the delivery of the device for treatment and the retraction after treatment. Other aspects of the improved medical device include features for holding the flexible substrate in place and preventing displacement during delivery and retraction. Other aspects of the improved medical device include features for holding the flexible substrate in a compact stowed configuration during treatment and for controlling the retraction of the flexible substrate after treatment to facilitate removal of the medical device. Additional aspects and advantages of these and other systems will become apparent from the following detailed description of the example embodiments performed with reference to the accompanying drawings. Summary of the invention

[0007] Various examples of systems for treating tissue are described herein. An example system may include a flexible substrate having a head portion and a foot portion, and also including a first peripheral side portion and a second peripheral side portion, both spanning between the head portion and the foot portion. The flexible substrate also includes a first arm segment extending outward from the head portion and a second arm segment extending outward from the foot portion. An electrode array is disposed on the flexible substrate, wherein at least a portion of the electrode array extends to one of the first arm segment or the second arm segment.

[0008] In some example systems, the first arm segment and the second arm segment are aligned relative to each other along a first axis, and the first axis extends across the flexible substrate from the head portion to the foot portion. In some example systems, the first arm segment and the second arm segment are aligned relative to each other along one of the first peripheral side portion or the second peripheral side portion of the flexible substrate. In some example systems, the first arm segment is substantially orthogonal to the head portion, and the second arm segment is substantially orthogonal to the foot portion. In some example systems, one of the first arm segment or the second arm segment does not have the electrode array. In some example systems, the first arm segment and the second arm segment are each formed as an integral part of the flexible substrate.

[0009] In some example systems, the flexible substrate may include one or more holes formed thereon, wherein the one or more holes are disposed between portions of the electrode array. In some example systems, the electrode array includes a first trace element and a second trace element offset from each other on the flexible substrate, and wherein at least some of the one or more holes are disposed on the flexible substrate between the first trace element and the second trace element.

[0010] In some example systems, the flexible substrate further comprises a top surface and an opposite bottom surface, wherein the first peripheral side portion of the flexible substrate comprises a first edge surface spanning from the top surface to the bottom surface, and wherein the second peripheral side portion of the flexible substrate comprises a second edge surface spanning from the top surface to the bottom surface, and the system further comprises a protective coating covering at least one of the first edge surface or the second edge surface of the flexible substrate. In some example systems, the protective coating covers at least a portion of the top surface of the flexible substrate and may also cover at least a portion of the electrode array disposed on the top surface of the flexible substrate. In some example systems, the protective coating covers an outer edge surface of the flexible substrate.

[0011] In some example systems, the length of the first perimeter side portion of the flexible substrate is different from the length of the second perimeter side portion of the flexible substrate. In some example systems, the length of the first perimeter side portion of the flexible substrate is greater than the length of the second perimeter side portion of the flexible substrate. In other example systems, the length of the first perimeter side portion of the flexible substrate is less than the length of the second perimeter side portion of the flexible substrate.

[0012] Another example system may include an elongated member and an expandable member, the expandable member coupled to the elongated member, wherein the expandable member is radially expandable relative to the elongated member. The system may also include a flexible substrate including an electrode array disposed thereon, the flexible substrate having a head portion and a foot portion and a first peripheral side portion and a second peripheral side portion each spanning between the head portion and the foot portion, the flexible substrate including a first arm segment extending outwardly from the head portion and a second arm segment extending outwardly from the foot portion, wherein when in a stowed position, the flexible substrate surrounds at least a portion of the expandable member, wherein one of the first arm segment or the second arm segment of the flexible substrate is coupled to the expandable member to hold the flexible substrate against the expandable member in the stowed position, and wherein the flexible substrate is expandable from the stowed position to a deployed position in response to radial expansion of the expandable member. In some example systems, when the flexible substrate is in the deployed position, the one of the first arm segment or the second arm segment is coupled to the expandable member.

[0013] In some example systems, the expandable member is coupled to a distal portion of the elongated member. In some example systems, at least a portion of the elongated member extends distally of the expandable member.

[0014] In some example systems, one or more wires are coupled to the electrode array and configured to provide power to the electrode array, wherein the one or more wires hold the flexible substrate in place along a proximal portion of the elongated member.

[0015] In some example systems, the elongated member includes a distal portion and a proximal portion, and wherein the expandable member is coupled to the elongated member between the distal portion and the proximal portion. In some example systems, the one of the first arm segment or the second arm segment of the flexible substrate is coupled to the expandable member near the distal portion of the elongated member to hold the flexible substrate against the expandable member. In some example systems, the other of the first arm segment or the second arm segment of the flexible substrate is coupled to one or more wires configured to power the electrode array, the one or more wires holding the flexible substrate against the expandable member near the proximal portion of the elongated member.

[0016] In some example systems, the flexible substrate further includes a front edge defined along one of the head portion or the foot portion of the flexible substrate, the front edge corresponding to the one of the first arm segment or the second arm segment that couples the flexible substrate to the expandable member when the flexible substrate is in the stowed position, and the system further includes a first pad adjacent to the front edge of the flexible substrate that prevents tissue trauma during system delivery. In some example systems, the first pad contacts the front edge of the flexible substrate. In some example systems, the flexible substrate further includes a rear edge defined along the other of the head portion or the foot portion of the flexible substrate, and the system further includes a second pad adjacent to the rear edge of the flexible substrate that prevents tissue trauma during system removal. In some example systems, the second pad contacts the rear edge of the flexible substrate.

[0017] In some example systems, the flexible substrate further comprises a rear edge defined along the other of the head portion or the foot portion of the flexible substrate, wherein the expandable member is partially expanded to form a second pad adjacent to the rear edge of the flexible substrate that prevents tissue trauma during system removal. In some example systems, the second pad contacts the rear edge of the flexible substrate.

[0018] Another example system includes an elongated member and an expandable member coupled to the elongated member, wherein the expandable member is radially expandable relative to the elongated member. The system may also include a flexible substrate including an electrode array disposed thereon, wherein the flexible substrate is movable from a stowed position, in which the flexible substrate surrounds at least a portion of the expandable member and has a first outer diameter, to a deployed position, in which the flexible substrate expands to a second outer diameter greater than the first outer diameter in response to radial expansion of the expandable member. An adjustment member is coupled to at least one of the flexible substrate or the expandable member, wherein the adjustment member is adjustable to maintain the flexible substrate in the stowed position.

[0019] In some example systems, the adjustment member is further adjustable to control movement of the flexible substrate from the stowed position to the deployed position after initial adjustment to maintain the flexible substrate in the stowed position. In some example systems, the adjustment member is further adjustable to drive the flexible substrate from the deployed position to the stowed position.

[0020] In some example systems, the flexible substrate further comprises one or more holes formed thereon, and wherein the adjustment member is coupled to the flexible substrate through at least some of the one or more holes. In some example systems, the adjustment member is a cable or wire that is woven through at least some of the one or more holes formed on the flexible substrate to couple the adjustment member to the flexible substrate.

[0021] In some example systems, the adjustment member is releasable from the flexible substrate to facilitate movement of the flexible substrate from the stowed position to the deployed position.

[0022] In some example systems, the adjustment member limits expansion of the flexible substrate in the deployed position to a predetermined outer diameter. In some example systems, the flexible substrate further comprises one or more holes formed thereon, and wherein the adjustment member is coupled to the flexible substrate through at least some of the one or more holes, the adjustment member contacts the flexible substrate to limit expansion to the predetermined outer diameter.

[0023] In some example systems, the flexible substrate is coupled to the expandable member, and wherein the adjustment member is coupled to the expandable member, wherein the adjustment member adjusts the expandable member to maintain the flexible substrate in the stowed position.

[0024] In some example systems, the adjustment member includes a tensioning element (such as a wire or cable), wherein the tensioning element adjusts the flexible substrate in response to tension applied to the tensioning element to maintain the flexible substrate in the stowed position. In some example systems, the tensioning element itself and / or the tension of the tensioning element may be releasable (such as via cutting of the tensioning element) to facilitate adjustment of the flexible substrate from the stowed position to the deployed position. In some example systems, the tensioning element drives the flexible substrate from the deployed position to the stowed position in response to tension applied to the tensioning element.

[0025] In some example systems, the flexible substrate further comprises one or more holes formed therein, and wherein the adjustment member is a tensioning element coupled to the flexible substrate through at least some of the one or more holes. In some example systems, the tensioning element is a cable or wire that is woven through at least some of the one or more holes formed on the flexible substrate to couple the tensioning element to the flexible substrate.

[0026] In some example systems, the flexible substrate further includes one or more holes formed therein, and the adjustment member is a tensioning element coupled to the flexible substrate through at least some of the one or more holes, the tensioning element contacting the flexible substrate to limit the expansion to the predetermined outer diameter.

[0027] Another example system for tissue treatment includes a flexible substrate having a proximal end and a distal end and a first peripheral side portion and a second peripheral side portion each spanning between the proximal end and the distal end. The system also includes an electrode array disposed on the flexible substrate, wherein the electrode array includes a plurality of spaced apart traces, wherein a first trace is closest to the proximal end of the flexible substrate and a second trace is closest to the distal end of the flexible substrate. The flexible substrate includes a buffer region without electrode traces, the buffer region being disposed between at least one of: a) a distance between the first trace and the proximal end of the flexible substrate; or b) a distance between the second trace and the distal end of the flexible substrate, and wherein a length of the buffer region is equal to or greater than a spacing between adjacent traces of the electrode array. In some example systems, the buffer region is between a) a distance between the first trace and the proximal end of the flexible substrate and b) a distance between the second trace and the distal end of the flexible substrate. In some example systems, a length of the buffer region between the first trace and the proximal end of the flexible substrate is greater than a length of the buffer region between the second trace and the distal end of the flexible substrate. In other example systems, the length of the buffer region between the first trace and the proximal end of the flexible substrate is less than the length of the buffer region between the second trace and the distal end of the flexible substrate. In some example systems, the length of the buffer region is in a range between 3 mm and 7 mm.

[0028] It should be understood that the foregoing summary provides various examples further described herein and is not intended to identify any key or important aspects of the disclosed or claimed subject matter. In addition, aspects of the example systems outlined above may be combined in any suitable manner without departing from the principles of the disclosed or claimed subject matter. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The foregoing and other features of the present disclosure will become more apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several examples of the present disclosure and are therefore not to be considered limiting of scope, the present disclosure will be described with additional specificity and detail through the use of the accompanying drawings, in which:

[0030] Figure 1is a schematic illustration of a system for electroporation and / or electrolysis according to examples described herein.

[0031] Figure 2 is a schematic illustration of a robotic-assisted manipulator system according to examples described herein.

[0032] Figure 3A is a schematic diagram of an instrument system according to examples described herein.

[0033] Figure 3B An example of an extended apparatus according to an example described herein is shown. Figure 3A The distal portion of the device system.

[0034] Figure 4A A catheter is illustrated in a sheath configuration, the catheter comprising an electrode array for delivery to a target area according to examples described herein.

[0035] Figure 4B An example of a device in a non-sheathed configuration according to an example described herein is shown. Figure 4A of the catheter.

[0036] Figure 5 Another catheter having an electrode array for delivery to a target area is illustrated according to examples described herein.

[0037] Figure 6 The diagram shows Figure 5 A separate flexible substrate for the electrode array of the catheter.

[0038] Fig. 7A A flexible substrate including a protective coating along an edge portion of the flexible substrate is illustrated according to examples described herein.

[0039] Figure 7B Another flexible substrate is illustrated according to examples described herein that includes a protective coating along an edge portion of the flexible substrate.

[0040] Figure 8 The diagram shows Fig. 7A An example catheter of a flexible substrate.

[0041] Fig. 9 Illustrated is a catheter having an electrode array with distal and proximal pads for minimizing trauma during delivery to a target area according to examples described herein.

[0042] Fig.10 A catheter having an electrode array is illustrated wherein distal and proximal portions of an expandable member are partially expanded to minimize trauma during delivery to a target area, according to examples described herein.

[0043] Fig.11A A catheter having an adjustment member operable to maintain a flexible substrate in a stowed position during delivery to a target area is illustrated according to examples described herein.

[0044] Fig. 11B A schematic diagram of a catheter having an adjustment member according to examples described herein is illustrated.

[0045] Fig. 11C Another schematic diagram of a catheter having an adjustment member according to examples described herein is illustrated.

[0046] Fig.11D Illustrated is a schematic diagram of a flexible substrate having an adjustment member for maintaining the flexible substrate in a stowed position during delivery to a target area according to examples described herein.

[0047] Fig.11E Another schematic diagram of a flexible substrate having an adjustment member for maintaining the flexible substrate in a stowed position during delivery to a target area is illustrated according to examples described herein.

[0048] Fig.11F A flexible substrate is illustrated according to examples described herein that includes one or more alignment members along an edge portion of the flexible substrate for holding the flexible substrate against an expandable member.

[0049] Fig.12 yes Fig.11A Schematic end view of a flexible substrate and an adjustment member.

[0050] Fig.13 Illustrated is a catheter having a keyed sheath operable to cooperate with a flexible substrate for retracting the flexible substrate to facilitate retracting the catheter when a procedure is completed, according to examples described herein.

[0051] Fig.14 is a schematic illustration of a segmented flexible substrate and electrode array system for use with a catheter according to examples described herein.

[0052] Fig.15 is a schematic illustration of a catheter according to examples described herein.

[0053] Fig.16A is a schematic illustration of a flexible substrate and an electrode array system surrounding an expandable member according to examples described herein.

[0054] Fig. 16B yes Fig.16ASchematic illustration of a flexible substrate illustrating a partially displaced electrode array system upon expansion of an expandable member according to examples described herein.

[0055] Fig. 16C is another schematic illustration of a flexible substrate having an electrode array system for use with a catheter according to examples described herein.

[0056] Fig.16D is yet another schematic illustration of a flexible substrate having an electrode array system for use with a catheter according to examples described herein. DETAILED DESCRIPTION

[0057] Certain details are set forth below to provide a full understanding of the embodiments of the present disclosure. However, it will be clear to those skilled in the art that embodiments of the present disclosure may be practiced without these specific details. In addition, the specific embodiments of the present disclosure described herein are provided as examples and should not be used to limit the scope of the claimed subject matter to these specific embodiments. In other cases, well-known materials, components, processes, controller components, software and / or anatomical structures are not described or shown in detail to avoid unnecessarily obscuring the embodiments.

[0058] The present disclosure relates to devices and systems for providing controlled delivery of one or more electrodes (e.g., one or more pairs of electrodes) to a target tissue site for treatment via a flexible substrate deployment. In general, a method for minimally invasive regenerative surgery is disclosed, which includes subjecting a target area in living tissue to ablation delivered via one or more pairs of electrodes. In some examples, the ablation energy can be in the form of a combination of one or more electric fields and electrolysis. However, it should be understood that the example systems and methods described herein can be used to deploy a flexible substrate carrying electrodes using an ablation modality other than electroporation and / or electrolysis (e.g., radiofrequency ablation).

[0059] During an example procedure utilizing electroporation and electrolysis, electrodes are brought into proximity and / or contact with the target tissue, and an electric field is generated by applying a voltage and / or current between one or more pairs of electrodes. The electric field can be generated to have a size that permeabilizes the cell membranes in the desired ablation region. The electric field can be generated to produce electrolytic products of a size that does not itself cause damage to cells or extracellular matrix located in and around the target treatment region. However, when sufficient electrolytic products are produced in the permeabilized cell region, cell death occurs in the region where the electric field is applied without damaging the extracellular matrix or scaffolding to help promote tissue re-growth in the treatment tissue region.

[0060] In some examples, after ablative energy is applied to one target area, the electrodes can be moved to other tissue locations by advancing and / or retracting the delivery catheter and the electrodes carried by the delivery catheter as needed and repeating the process. In this way, electroporation and electrolysis can be performed at multiple locations within the patient to cover a larger area of ​​tissue. In some examples, multiple sets of electrodes can be positioned at multiple corresponding tissue sites so that electroporation and electrolysis can be performed in parallel at each site, thereby reducing and / or eliminating the need to repeat the procedure as the catheter moves through the patient.

[0061] After ablation using electroporation and electrolysis, with the help of the extracellular matrix left, tissue regeneration can occur at the treatment site. Tissue can be regenerated from stem cells introduced into the treatment site via the circulatory system, from stem cells found at the edge of the ablated tissue, and / or from cells or other components otherwise introduced into the treatment site. Then stem cells proliferate along the complete extracellular matrix and enter the ablation zone to replace the ablated tissue with healthy tissue. Although regeneration can be achieved at the treatment site by natural processes, there are other methods to refill the extracellular matrix with cells that are different from the original cells of the location. For example, genetically engineered cells can be injected into the treatment site to promote regrowth. This process may be useful in the case where the original tissue cells have genetic or other abnormalities. In another example, other cells (e.g., pancreatic islets) can be introduced into the treatment site for implantation and proliferation. In other embodiments, other methods can be used to promote tissue regeneration at the treatment site.

[0062] In some embodiments of the present disclosure, the systems and methods disclosed herein can be used to treat gastrointestinal tissue. In other embodiments, any of a variety of tissues can be treated using the systems and methods described herein. Generally, tissues that expect tissue regeneration or expect to replace one type of cell with another type of cell can be treated. Examples include intestines, duodenum, stomach, bladder, uterus, endometrial lining, ovaries, colon, rectum, sinuses, ducts in the body, ureters, prostate, skin, muscles, nerves, diaphragms, momentum, kidneys, follicles, brain, lymphatic vessels, breasts, esophagus, lungs, liver, kidneys, lymph nodes, lymph node basins and / or hearts. Replacing one type of tissue with another type of tissue can be in an area where it is expected to replace fibrotic cells with stem cells that can re-regulate fibrotic areas, or when islets are injected into a portion of the liver to produce a new source of insulin. In other examples, other tissues can be treated. Additional details related to an example process of electroporation and / or electrolysis for tissue treatment according to some embodiments are provided below.

[0063] As described above, electroporation can be performed to permeabilize the cell membrane of the target cell. Reversible electroporation can be used, wherein after removing the electric field, permeabilization can be stopped. Cells can survive in reversible electroporation, wherein the holes in the membrane are resealed and restored to a steady state. In irreversible electroporation, the permeabilization of the cell membrane is permanent, resulting in cell death. Generally for biological tissues, electric fields below about 1500V / cm to about 200V / cm are considered to produce reversible electroporation, while electric fields above about 1500V / cm are considered to produce irreversible electroporation. The examples of the systems and methods described herein can utilize reversible electroporation to avoid the shortcomings of irreversible electroporation, which can include heating and thermal damage, the complexity of providing such a large electric field, and muscle contraction that may be caused by a large electric field. It should be understood that although the systems and methods described herein can be designed to utilize reversible electroporation, there may be a position or accidental area where the condition is such that irreversible electroporation or even thermal ablation can occur in a limited portion of the treated tissue.

[0064] In some treatment procedures, the electrolysis product can be applied to permeabilized cells to cause cell death of permeabilized cells in the applied electric field while keeping the extracellular matrix of permeabilized cells intact. Extracellular matrix generally refers to a three-dimensional network of proteins and / or other molecules (such as collagen fibers, proteoglycans and / or proteins (such as fibronectin and / or laminin)), which provides structure for cells and tissues, and can provide signals for cell growth and development in addition. Extracellular matrix can be used as a scaffold for tissue regeneration and / or engineering. For example, cells can be regenerated, grown, transplanted or otherwise cultivated on the extracellular matrix. By retaining the extracellular matrix in the region of otherwise ablated cells described herein, cell regeneration and / or tissue engineering can occur in the region of ablated cells. In some programs, the extracellular matrix can be transplanted from one region of ablated cells to another region (which can be another region of ablated cells) to promote regeneration and / or tissue engineering in the transplanted region. In some cases, once there is an extracellular matrix, material can be injected into the extracellular matrix to enhance regrowth.

[0065] Therefore, one aspect of the ablation techniques applicable to the present disclosure relates to the use of electrolysis during the ablation process. The electrolysis process refers to an electrochemical reaction occurring at the electrode surface of an electrode in contact with an ionically conductive medium (e.g., an aqueous solution, including a natural physiological concentration solution present in tissue). Electrochemical reactions usually occur due to the transfer between electrons from the electrode and ions or atoms in the solution driven by a potential. Chemical substances produced on the electrode diffuse outward from the electrode in the ionically conductive medium during electroosmotic diffusion. In a typical environment of biological substances, these chemical reactions also produce changes in pH, resulting in acidic regions near the anode and alkaline regions near the cathode and the production of chemicals that may be toxic to biological substances. These products and changes in pH diffuse from the electrode into the biological medium. Electrolysis alone (e.g., without cell membrane permeabilization) is a well-known chemical ablation mechanism, and the extent of ablation is a function of the nature of the chemical substance and its concentration. Because the electrolysis products are produced at the electrode, in order to ablate a large amount of biological substances, the electrolysis products must diffuse throughout the target volume. Diffusion is a relatively slow process, making electrolytic ablation using electrolysis alone to ablate result in a lengthy procedure. For example, electrolysis products and tissue ablation treatment using electrolysis alone may occur over a time period on the order of tens of minutes to hours. This is because the concentration of electrolytic cytotoxic products must diffuse throughout the target volume to ablate the volume. In addition, when electrolysis is used alone to ablate tissue, the concentration of electrolysis products and exposure time are such that scarring, ulceration, coagulative necrosis and / or fibrosis occurs.

[0066] Electrolysis preferably uses inert electrodes that do not participate in the electrolysis process except as a source or sink of electrons or as a catalyst. When participating non-inert electrodes are used in the process, they may produce metal ions that may cause systemic damage to the body, such as excess iron or even metal fragments. The electrolysis products may include cytotoxic products. For example, large amounts of protons H + A non-physiological acidic environment can be generated by diffusion from the anode, and a large amount of OH -The non-physiological alkaline environment diffused from the cathode can be produced. The permeabilized cells exposed to non-physiological pH can die because the intracellular homeostasis is destroyed, and the normal cell chemical path is destroyed. The electrolysis product can combine and produce cytotoxic chemicals, such as hypochlorous acid or hydrochloric acid, and its influence may depend in part on the pH in the region where they are formed. For example, a saline solution (NaCl and H2O) with a pH between 3 and 5 is made to pass through an electric current. The highly toxic hypochlorous acid (HOCl) may be produced. The electrolysis product affects biological substances according to its concentration and exposure time by the chemical reaction involving them. High concentrations and long-term exposure to the electrolysis product affect all biomolecules in the target tissue, the undesirable influence for tissue regeneration applications. However, it is wise to deliver the electrolysis product with lower concentrations in a shorter time period with the electrolysis product not affecting all biomolecules in the tissue volume disposed and only being able to affect its membrane by diffusing into the cell and affecting the intracellular homeostasis and the level of the temporarily or permanently permeabilized cell can cause cell death without affecting the extracellular matrix. For example, a typical method for tissue ablation by electrolysis uses a target tissue per centimeter diameter to deliver about 30-100 coulombs of charge, and typically delivers 40mA within 90 minutes. In some systems for regenerative electrolytic electroporation ablation, an exponentially decaying current with a decay amplitude (in one example, a peak value of 250mA is delivered in less than 2ms) in a much shorter time can be used. Therefore, the current provided for electrolysis can be provided using an exponential decay or other decay waveform, and can have an amplitude of about tens or hundreds of mA. The current can be provided on a time scale of about milliseconds, or can be provided with multiple pulses (e.g., multiple waveforms).

[0067] The example systems and methods described herein can utilize electrolysis products to cause cell death while utilizing electroporation to permeabilize the cell membrane. The electrolysis products are sufficient to ablate (e.g., cause cell death) permeabilized cells within a relatively short time frame. However, the concentration and exposure time of the electrolysis products are not sufficient to cause cell death of non-permeabilized cells, thereby minimizing or avoiding the formation of scar tissue, fibrotic tissue or ulcers in the treatment area. Scar tissue and fibrosis are indications that the extracellular matrix has been affected, and the ability of cell regeneration and / or tissue engineering transformation occurring in the ablation area may be suppressed. Therefore, the electrolysis products are only used to ablate permeabilized cells while keeping the extracellular matrix intact to promote tissue regrowth.

[0068] Examples of systems disclosed herein may include electrodes, power supplies, and controllers to apply electrolysis and / or electroporation to treat internal tissues. The controller may control the charge delivered to the electrode to induce one or more electric fields. For example, the electrode may be used to generate a current to produce an electrolysis product and a voltage difference to produce an electric field that induces electroporation. The duration and magnitude of the applied charge may determine the dosage of the electrolysis product and the degree of permeabilization of cells in the treatment site. Therefore, the area of ​​cell ablation may be determined by the area in which the cell is exposed to a combination of permeabilization and electrolysis products that cause ablation. However, ablation may keep the extracellular matrix intact in the area of ​​the ablated cell to which the electric field has been applied. The composition of the electrode may be selected according to the desired product produced and the desired electroporation effect.

[0069] refer to Figure 1 , a brief overview of an example system for delivering a catheter having electrodes to a target tissue site for treatment via electroporation and / or electrolysis is provided below. For clarity, the written description of various example embodiments and the associated drawings generally refer to catheters for use with the systems and methods described herein. However, it should be understood that other suitable medical devices (e.g., devices that may not be specifically classified as catheters) and other suitable energy modalities (e.g., radiofrequency ablation) may be used in conjunction with the disclosed systems and methods without departing from the principles of the disclosed subject matter.

[0070] Figure 1 is a schematic illustration of a system 10 arranged according to an example embodiment described herein. In general, the example systems described herein may include a delivery system and a controller. Figure 1 In the example of FIG. 1 , system 10 includes controller 14 and catheter 40. Examples of other suitable catheters that can be used with system 10 are referenced below. Figures 4A-16D Detailed description further. As further described below, in some examples, controller 14 may include processor 16, computer readable medium 18, and other computing system components, such as one or more input devices, output devices, sensors, and / or communication devices. In other examples, additional, fewer, and / or different components may be used. Computer readable medium 18 includes executable instructions 20 for causing electroporation and electrolysis using catheter 40, and may include stored parameters 22 that may be used in the process for causing electroporation and electrolysis, such as electric field strength, voltage and / or current levels, waveform shape, exposure duration parameters, and any other suitable parameters. Figure 1 In the example of FIG. 4 , a circle depicted around the end of catheter 40 may indicate a region of cells that may be permeabilized via an applied electric field.

[0071] The controller 14 can be implemented using a computing device. Examples of computing devices include controllers, microcontrollers, computers, servers, medical devices, smart phones, tablet computers, wearable devices, etc. The computing device can be handheld and can also have other uses. The controller 14 can include one or more processors, such as processor 16. There can be any type or number of processors, including one or more central processing units (CPUs) or graphics processing units (GPUs) with any number of cores, controllers, microcontrollers, and / or custom circuits, such as one or more application specific integrated circuits (ASICs) and / or field programmable gate arrays (FPGAs).

[0072] The controller 14 described herein may include a computer readable medium 18, such as a memory. Any type or kind of memory may be present (e.g., read-only memory (ROM), random access memory (RAM), solid-state drive (SSD), secure digital card (SD card), etc.). Although Figure 1 A single block is depicted as computer readable medium 18 in FIG. 1 , but there may be any number of computer readable medium 18 devices. Computer readable medium 18 may be in communication with processor 16 (eg, electrically connected to processor 16 ).

[0073] As described above, computer readable medium 18 may store executable instructions for execution by processor 16, such as executable instructions 20 for causing electroporation and electrolysis using catheter 40, and may utilize stored parameters 22 of catheter 40. In this manner, techniques for applying electroporation and electrolysis in tissue may be implemented herein, in whole or in part, in software.

[0074] Executable instructions 20 may include instructions for controlling the charge delivered to an electrode, such as electrode 50 of catheter 40. Thus, controller 14 may induce a voltage difference across the target tissue to generate an electric field that causes permeabilization of cells in the tissue region targeted for treatment. In the illustrated embodiment, electrode 50 may be disposed on a flexible substrate (e.g., Figure 4A On a flexible substrate 312), as specifically referenced Figure 4A and Figure 4B The electrode 50 is illustrated in a cavity or lumen 32 formed in the tissue 30. Although the catheter 40 is shown as being disposed in the lumen 32 of the tissue 30, the catheter 40 may be on the surface of the tissue 30, inside the tissue 30, and / or near the tissue 30. In addition, although the catheter 40 is shown for delivering and positioning the electrode 50 for permeabilizing and / or generating electrolytic products to treat the tissue 30, in other embodiments, other suitable delivery systems may be used.

[0075] Controllers (such as Figure 1The controller 14 of the present invention can activate one or more selected electrodes 50 to provide an electric field. In some embodiments, the controller 14 can alternately or otherwise select a pattern of activated electrodes 50 (e.g., activating electrode pairs in sequence) to shape or deliver a specific electric field. In some examples, a fluid or other substance can be injected into the tissue 30, contacted with the tissue 30, or otherwise placed in or around the tissue 30 to help shape the electric field generated in the tissue 30. For example, a conductive fluid can help shape the field (e.g., by expanding the field). In other examples, a non-conductive fluid can help shape the field (e.g., by attenuating the field). In some examples, a non-conductive fluid or other substance can be injected or otherwise placed in the tissue to protect areas where ablation is not desired. The electric field may not penetrate and / or be carried through the non-conductive fluid, so that the field does not reach the tissue where ablation is not desired, or at least exists at an intensity insufficient to cause permeabilization or other cellular changes.

[0076] The controller 14 can also be used to induce an electric current through the tissue 30, such as between the electrodes 50, to produce electrolytic products. The electrolytic products can cause ablation of permeabilized cells, but are preferably insufficient to destroy the extracellular matrix in the area of ​​the permeabilized cells. The remaining intact extracellular matrix can allow tissue regeneration and tissue engineering as previously described.

[0077] In some embodiments, one or more electrodes 50 used to apply electroporation can also be used to produce electrolysis products (in other words, some or all electrodes can be used for both electroporation and electrolysis). In other embodiments, the first subset of electrodes 50 used to apply electroporation can be different from the second subset of electrodes 50 used to produce electrolysis products.

[0078] In some embodiments, the power source 12 is integrated with the controller 14. The power source 12 can be implemented using any suitable power source, such as one or more AC power sources, DC power sources, batteries, and / or waveform generators. The power source 12 can supply power / electricity / power to the electrode 50 to generate a voltage and / or current in the tissue 30, and thus generate an electric field and / or electrolysis products. In some examples, the power source 12 can be implemented using a signal generator, such as an exponential decay wave generator (e.g., Harvard Apparatus BTX 630), however, the present disclosure is not limited thereto or thereby.

[0079] Controller 14 can control the timing, intensity, and duration of the electric field and / or electrolysis products provided via catheter 40. Controller 14 can, for example, be programmed to provide electronic signals to catheter 40 via power source 12, wherein the electronic signals can indicate a dose of treatment, such as a dose of electrolysis products and / or a permeabilization level of cells. The electronic signals can control the timing and magnitude of the generated electric field, which can allow a user to customize the treatment of tissue 30 as desired. In some embodiments, controller 14 can include such a program, or include one or more processing devices (e.g., processors) coupled to a computer-readable medium 18, wherein the computer-readable medium 18 is encoded with executable instructions 20 for electrolysis and permeabilization. Although in Figure 1 Controller 14 is shown as a separate component coupled to catheter 40, but in some embodiments, controller 14 may be integrated as part of catheter 40. In other embodiments, controller 14 may include programmable circuitry coupled to catheter 40 via a wired or wireless connection.

[0080] As previously described, the system 10 may include any suitable parameters 22 for controlling various aspects of the electroporation and electrolysis process, such as electric field strength, voltage level, current level, waveform shape, exposure duration parameters, and any other suitable parameters. The parameters 22 may be stored in the computer-readable medium 18 or in other suitable databases in communication with the controller 14. In some embodiments, the controller 14 may be used to calculate the parameters 22, or the controller 14 may communicate with another system operable to calculate the parameters 22.

[0081] In some example embodiments, the parameters 22 for a particular treatment protocol can be determined based on measurements taken in the tissue of interest or from different samples of similar tissues. For example, measurements can be taken at various voltage levels using a particular electrode configuration, and a target voltage level, current, pulse pattern, time constant, and other factors that cause reversible electroporation and delivery of electrolytic products to cause cell death of permeabilized cells as desired can be identified.

[0082] In some embodiments, examples of parameters 22 that can be used include the delivery of between 1 and 10 voltage pulses between 100V and 1000V. These pulses can be delivered in a system with a capacitance between 50μF and 100μF and a resistance between 15-20 ohms. The amount of electrolytic product produced can be related to the delivered charge in coulombs. There are several ways to calculate the delivered charge. For example, the charge stored in the capacitor Q (in coulombs, abbreviated as C) is equal to the product of the capacitance C of the capacitor (in farads, abbreviated as F) and the voltage V (in volts, abbreviated as V) across its terminals. That is, Q=C·V. In addition, the current I (in amperes, abbreviated as A) multiplied by the time t=charge. I*t=Q. By defining the capacitance and the voltage across the capacitance, the charge can be defined, and the electrolytic performance is therefore determined. When the capacitor discharges, it generates a current, and the current multiplied by the time must be equal to the charge in the capacitor. When the capacitor discharges, the current is not constant-it decays exponentially. Therefore, the time measurement is given as an exponential decay time constant. The capacitor that controls the time constant is usually connected from a power source (such as Figure 1 The power supply 12) is obtained by a capacitor included in the power supply 12).

[0083] In some embodiments, the time constant (e.g., the exponential decay time constant of the capacitor discharge) can be between 1.7 milliseconds (ms) and 1.8 milliseconds. In other embodiments, the time constant can be in the range of 50 microseconds (μs) to 3 ms. Typically, the lower limit of the time constant is related to the time sufficient to ensure that the electrolytic substance (e.g., electrolysis product) permeates the target area of ​​the permeabilized cell. The upper limit of the time constant is generally related to the generation of the electrolytic substance (e.g., electrolysis product) that can itself cause ablation. Therefore, electrolysis is generally targeted at the amount of time sufficient to allow the electrolytic product to diffuse through the area of ​​the permeabilized cell. However, the amount of time for providing electrolysis should be limited to ensure that the process does not result in ablation of non-permeabilized cells or otherwise damage the extracellular matrix in the area of ​​the ablated cells.

[0084] In some embodiments, the electric field generated ranges from 100 V / cm to 3500 V / cm. In other embodiments, the electric field can be between 100 V / cm and 1500 V / cm or between 200 V / cm and 850 V / cm. In other embodiments, the electric field can be less than 1400 V / cm in some examples, less than 1300 V / cm in some examples, less than 1000 V / cm in some examples, less than 800 V / cm in some examples, or less than 600 V / cm in some examples.

[0085] The system 10 may also include one or more sensors (not shown) for measuring the pH, temperature, electric field strength, tissue resistivity or impedance, and / or other suitable properties of the tissue 30 in order to optimize the treatment. For example, in one embodiment, a pH sensor may be combined with the system 10. The pH sensor may be arranged in any of several configurations, such as being coupled to the catheter 40 adjacent to the electrode 50 to detect the pH value near the electrode 50. In another embodiment, the pH sensor may be provided at the outer edge of the target area of ​​the tissue. In either configuration, the pH sensor may communicate with the controller 14, wherein the controller 14 may utilize one or more received pH values ​​as an indication of tissue ablation and / or monitor the occurrence of tissue damage based on the pH level detected at the treatment site and the surrounding area of ​​the tissue. In some embodiments, the controller 14 may adjust the voltage, current, and / or electric field applied to the tissue in response to the detected pH level. For example, if the pH value of the tissue outside the treatment site is at or exceeds a threshold value for tissue damage, the controller 14 may reduce the size of the electric field, the duration between pulses, or stop applying the electric field. Similarly, if the pH of tissue within the target area is at or above the threshold for tissue ablation, controller 14 may stop applying current through the electrodes to stop the electrolysis process, either immediately and / or after a desired elapsed electrolysis time.

[0086] In some embodiments, a resistivity meter can be used to determine the resistance of the target tissue. For example, Figure 1 The controller 14 and / or power source 12 of the system 10 can provide impedance measurements. The impedance measurements can determine the resistivity of the tissue 30 contacted by the electrodes 50 of the system 10. For example, the controller 14 and / or power source 12 can provide a nominal amount of current (such as a DC current) through the tissue 30, and receive the resistivity measurement and / or calculate the resistivity of the tissue 30. In some examples, the voltage, current, and / or electric field applied can be selected, determined, and / or allowed based on the measured resistance of the tissue 30. In some examples, multiple pulses of applied voltage can be selected, determined, and / or otherwise used based on the measured resistance of the tissue.

[0087] In some embodiments, sensors for detecting and / or determining electric field strength, such as gauss meters and / or tesla meters, may also be used. In such embodiments, the sensors may be in operable communication with controller 14 to ensure that the electric field strength remains at a target level for the desired treatment regimen.

[0088] In some embodiments, an ablation device (e.g., Figure 1The catheter 40) can be delivered via a computer-assisted, remotely operated manipulator system, which is sometimes referred to as a robot-assisted system or a robotic system. The manipulator system includes one or more manipulators that can be operated with the assistance of an electronic controller (e.g., a computer) to move and control the functions of one or more instruments when one or more instruments are coupled to the manipulator. Figure 2 One example embodiment of a robotic-assisted manipulator system 100 for use with the systems and methods described herein is illustrated. The manipulator system may be used, for example, in surgical, diagnostic, therapeutic, biopsy, or non-medical procedures.

[0089] refer to Figure 2 , the robot-assisted manipulator system 100 may include one or more manipulator assemblies 102 for operating one or more medical device systems 104 when performing various procedures on a patient P on a table T located in a medical environment 101. For example, the manipulator assembly 102 can drive the movement of a catheter or end effector, can apply treatment to a target tissue, and / or can manipulate a control member. The manipulator assembly 102 can be a remotely operated, non-remotely operated, or hybrid remotely operated and non-remotely operated assembly with selected degrees of freedom of motion that can be motorized and / or remotely operated and selected degrees of freedom of motion that can be non-motorized and / or non-remotely operated. An operator input system 106 that can be inside or outside the medical environment 101 typically includes one or more control devices for controlling the manipulator assembly 102. The manipulator assembly 102 supports the medical device system 104 and may optionally include a plurality of actuators or motors that drive input ends on the medical device system 104 in response to commands from a control system 112. The actuator may optionally include a drive system that, when coupled to the medical device system 104, advances the medical device system 104 into a naturally or surgically created anatomical orifice. Other drive systems can move the distal end of the medical device system 104 with multiple degrees of freedom, which may include three linear motions (e.g., linear motions along the X, Y, Z Cartesian axes) and three rotational motions (e.g., rotations around the X, Y, Z Cartesian axes). The manipulator assembly 102 may support various other systems for flushing, disposal, or other purposes. Such systems may include fluid systems (including, for example, reservoirs, heating / cooling elements, pumps, and valves), generators, lasers, interrogators, and ablation components.

[0090] The robot-assisted manipulator system 100 also includes a display system 110 for displaying images or representations of the surgical site and the medical instrument system 104 generated by the imaging system 109, which may include an imaging system such as an endoscopic imaging system. The display system 110 and the operator input system 106 may be oriented so that the operator O can control the medical instrument system 104 and the operator input system 106 with a telepresence perception. The graphical user interface may be capable of being displayed on the display system 110 and / or a display system of a separate planning workstation.

[0091] In some examples, the endoscopic imaging system components of imaging system 109 can be integrally or removably coupled to medical instrument system 104. However, in some examples, a separate imaging device (such as an endoscope) attached to a separate manipulator assembly can be used with medical instrument system 104 to image a surgical site. Endoscopic imaging system 109 can be implemented as hardware, firmware, software, or a combination thereof that interacts with or is otherwise executed by one or more computer processors, which can include a processor of control system 112.

[0092] The robot-assisted manipulator system 100 may also include a sensor system 108. The sensor system 108 may include a position / positioning sensor system (e.g., an actuator encoder or an electromagnetic (EM) sensor system) and / or a shape sensor system (e.g., a fiber optic shape sensor) for determining the position, orientation, speed, velocity, posture, and / or shape of the medical device system 104. The sensor system 108 may also include temperature, pressure, force, or contact sensors, etc.

[0093] The robot-assisted manipulator system 100 may also include a control system 112. The control system 112 includes at least one memory 116 and at least one computer processor 114 for implementing control between the medical device system 104, the operator input system 106, the sensor system 108, and the display system 110. The control system 112 also includes programming instructions (e.g., a non-transitory machine-readable medium storing instructions) for implementing procedures using the robot-assisted manipulator system, including for navigation, steering, imaging, deployment or retraction of engagement features, application of treatment to target tissue (e.g., via application of energy), etc.

[0094] The control system 112 may also optionally include a virtual visualization system to provide navigation assistance to the operator O when controlling the medical device system 104 during an image-guided surgical procedure. Virtual navigation using the virtual visualization system can be based on a preoperative or intraoperative data set of an anatomical pathway acquired with reference. The virtual visualization system processes images of the surgical site imaged using imaging techniques (such as computed tomography (CT), magnetic resonance imaging (MRI), fluoroscopy, thermal imaging, ultrasound, optical coherence tomography (OCT), thermal imaging, impedance imaging, laser imaging, nanotube X-ray imaging, etc.). The control system 112 can use the preoperative images to locate the target tissue (using visual imaging techniques and / or by receiving user input) and create a preoperative plan, including an optimal first positioning for performing the treatment. The preoperative plan may include, for example, a planned size of an extended expandable device, a treatment duration, a treatment temperature, and / or multiple deployment positions.

[0095] Figure 3A A medical device system 200 is illustrated according to some example embodiments. The medical device system 200 may be used for image-guided medical procedures. In some embodiments, the medical device system 200 may be used for non-teleoperated exploratory procedures or procedures involving traditional manually operated medical devices, such as endoscopy. In other embodiments, the medical device system 200 may be used with Figure 2 The medical device system 104 is interchangeable, or Figure 2 Variations of the medical device system 104 .

[0096] The medical device system 200 includes an elongated flexible device 202, such as a flexible catheter, an endoscope (e.g., a gastroscope, a bronchoscope, a duodenoscope), or other suitable device coupled to a drive unit 204. The elongated flexible device 202 includes a flexible body 216 having a proximal portion 217 and a distal portion 218, the distal portion 218 including a tip portion. In some embodiments, the flexible body 216 has an outer diameter of approximately 14-20 mm. Other embodiments of the flexible body 216 can have a larger or smaller outer diameter. The flexible body 216 can have an appropriate length to reach certain portions of the anatomical structure, such as the lungs, sinuses, throat, or upper or lower gastrointestinal tract regions when the flexible body 216 is inserted into the oral or nasal cavity of the patient.

[0097] The medical device system 200 optionally includes a tracking system 230 for determining the position, orientation, speed, velocity, posture, and / or shape of the distal portion 218 and / or one or more segments 224 along the flexible body 216 using one or more sensors and / or imaging devices. The entire length of the flexible body 216 between the distal portion 218 and the proximal portion 217 can be effectively divided into the segments 224. The tracking system 230 can optionally be implemented as hardware, firmware, software, or a combination thereof that interacts with or is otherwise executed by one or more computer processors, which can include Figure 2 A processor of the control system 112 in the system.

[0098] Tracking system 230 may optionally track distal portion 218 and / or one or more segments 224 using shape sensor 222. In some embodiments, tracking system 230 may optionally and / or additionally track distal portion 218 using position sensor system 220, such as an electromagnetic (EM) sensor system. In some examples, position sensor system 220 may be configured and positioned to measure six degrees of freedom (e.g., three position coordinates X, Y, Z and three orientation angles of pitch, yaw, and roll indicating a base point) or five degrees of freedom (e.g., three position coordinates X, Y, Z and two orientation angles of pitch and yaw indicating a base point).

[0099] The flexible body 216 includes one or more channels (eg, passageways) sized and shaped to receive one or more medical devices 226. In some embodiments, the flexible body 216 includes two channels 221 for individual devices 226, however, a different number of channels 221 may be provided. Figure 3B2 is a simplified schematic diagram of an end portion of a flexible body 216 having a medical device 226 extending outward therefrom according to some embodiments. In some embodiments, the medical device 226 can be used for procedures and aspects of procedures, such as surgery, biopsy, ablation, mapping, imaging, lighting, irrigation, or suction. The medical device 226 can be deployed through the channel 221 of the flexible body 216 and used at a target location within the anatomical structure. The medical device 226 may include, for example, an image capture device, a biopsy instrument, an ablation instrument, a catheter, a laser ablation fiber, and / or other surgical, diagnostic, or therapeutic tools. The medical tool may include an end effector with a single working member, such as a scalpel, a blunt blade, a lens, an optical fiber, an electrode, etc. Other end effectors may include, for example, forceps, graspers, balloons, needles, scissors, clip applicators, etc. Other end effectors may also include electrically activated end effectors, such as electrosurgical electrodes, expandable ablation members, transducers, sensors, imaging devices, etc. The medical device 226 can be advanced from the opening of the channel 221 to perform a procedure (e.g., electroporation and / or electrolysis in the present disclosure), and then retracted into the channel 221 when the procedure is completed. The medical device 226 can be removed from the proximal portion 217 of the flexible body 216 or from another optional instrument port (not shown) along the flexible body 216. The medical device 226 can be used with an image capture device (e.g., an endoscopic camera) that is also within the elongated flexible device 202. Alternatively, the medical device 226 itself can be an image capture device.

[0100] The medical device 226 may additionally house cables, linkages, or other actuation controls (not shown) extending between its proximal portion 217 and distal portion 218 to controllably bend the distal portion 218 of the medical device 226. The flexible body 216 may also house cables, linkages, or other steering controls (not shown) extending between the drive unit 204 and the distal portion 218 to controllably bend the distal portion 218, as shown, for example, by a dashed line depiction 219 of the distal portion 218. In some examples, at least four cables are used to provide independent "up and down" steering to control the pitch motion of the distal portion 218 and "side to side" steering to control the yaw motion of the distal portion 218. In embodiments where the medical device system 200 is actuated by a robotically assisted assembly, the drive unit 204 may include a drive input that is removably coupled to and receives power from a drive element (such as an actuator) of a remotely operated assembly. In some embodiments, the medical device system 200 may include gripping features, manual actuators, or other components for manually controlling the movement of the medical device system 200. Information from the tracking system 230 may be sent to the navigation system 232, where it is combined with information from the visualization system 231 and / or preoperatively acquired models to provide real-time position information to the physician or other operator.

[0101] In some embodiments, the medical device system 200 can be guided manually or via the robot-assisted manipulator system 100 to deliver the medical device 226 to the target tissue site for treatment. In some programs, the selection between manual or robot delivery and approach can be determined based on the medical application. For example, in some gastrointestinal applications, the medical device system 200 (or independent medical device 226) can be delivered intracavitary via a manual or robot delivery device through the oral or anal approach. It is also possible to use an abdominal approach with an integrated monopolar or bipolar instrument, a drop-in probe, or via a catheter. For urology applications, the medical device system 200 (or independent medical device 226) can be delivered intracavitary via a manual or robot delivery device through the urethra, perineum, preperitoneum, or abdomen using an integrated bipolar instrument, a drop-in probe, or via a catheter. Similarly, for gynecological applications, the medical device system 200 (or independent medical device 226) can be delivered via a manual or robotic delivery device through a vaginal approach, perineum or abdominally using an integrated bipolar instrument, a drop-in probe or via a catheter lumen. For hepatobiliary applications, the medical device system 200 (or independent medical device 226) can be delivered via a manual or robotic delivery device through an oral approach lumen to reach the ampulla or enter the liver from the outside via a gastrointestinal wall route, or using an integrated bipolar instrument, a drop-in probe or via a catheter abdominal delivery. For neurovascular applications, the medical device system 200 (or independent medical device 226) can be delivered via a manual or robotic delivery device through an intravascular approach or by a keyhole craniotomy with an integrated bipolar instrument, a drop-in probe or via a catheter. For cardiac applications, the medical device system 200 (or independent medical device 226) can be delivered via a manual or robotic delivery device through an intravascular approach or through the chest using an integrated bipolar instrument, a drop-in probe or via a catheter.

[0102] Common Reference Figures 4A-16D , the following provides references that can be used in conjunction with the previous reference Figure 1-Figure 3B Additional details of various catheter designs and embodiments and features of various components thereof for use with the described system 10, the robotic-assisted manipulator system 100, and / or the medical device system 200 are provided. Figures 4A-16D The described catheters are designed to facilitate their delivery to the target tissue site and to assist in the retraction of the components after treatment, while preventing potential trauma or damage to surrounding tissue during catheter delivery and retraction. Other features and advantages of the catheter design are further described below with reference to the accompanying drawings. As previously stated, although the following description and related drawings specifically relate to catheter designs, other suitable medical devices (e.g., non-catheter devices) may be used without departing from the principles of the disclosed subject matter.

[0103] Figure 4A and Figure 4B A catheter 300 is collectively illustrated in a sheath configuration and a sheathless configuration, respectively, according to an example embodiment, the catheter 300 being operable to deliver an electrode array 314 to a target tissue region (eg, Figure 1 The catheter 300 can be respectively connected to Figure 2 and Figure 3A The medical device systems 104 and 200 are used together to provide electrolysis and electroporation treatment according to example embodiments of the present disclosure. Figure 4A and Figure 4B , the catheter 300 includes an elongated member 302, such as a shaft or other member having a generally tubular profile, having a distal end 304 and a proximal end 305. The catheter 300 may include a sheath 306 surrounding a portion of the elongated member 302, the sheath 306 having a lumen 308 extending therethrough (see Figure 4B In some embodiments, the length of the elongated member 302 may be at least 85 cm, preferably 180 cm, and the diameter of the elongated member 302 may be approximately 5-7 mm, preferably 6 mm at its maximum outer diameter, so as to be consistent with the previously described references. Figure 3A and Figure 3B The catheter 300 is introduced in a similar manner as described through a working channel (e.g., working channel 221) of an endoscope or other suitable medical device system 200. It should be understood that in other embodiments, the elongated member 302 can have any suitable size that can depend on the size of the endoscope or other suitable device used to introduce the catheter 300 for delivery to the target tissue area.

[0104] The catheter 300 also includes an expandable member 310 coupled to the elongated member 302. The expandable member 310 can be coupled to the elongated member 302 between its distal end 304 and proximal end. Figure 4B As shown, in some embodiments, in the sheathless configuration, the expandable member 310 can be adjacent to the distal end 304. In other embodiments, the expandable member 310 can alternatively be distal to the elongated member 302, such that no portion of the elongated member 302 extends forward of the expandable member 310.

[0105] In the illustrated embodiment, expandable member 310 is illustrated as an expandable balloon. In some embodiments, the balloon can be a compliant balloon made of polyurethane, silicone, or other suitable material designed to expand several times its nominal size. In other embodiments, the balloon can be a semi-compliant balloon made of polyurethane or other suitable material designed to expand less than a compliant balloon. In other embodiments, other expandable members can be used, such as a braided mesh, an expandable frame, etc.

[0106] Expandable member 310 is radially expandable relative to elongated member 302 and can be expanded in a variety of different ways. For example, in some embodiments, expandable member 310 can be inflated with a fluid (such as air or another gas), a liquid (such as saline, a radiopaque solution, etc.). In some embodiments, a fluid can be introduced into expandable member 310 through a lumen (not shown) of elongated member 302. Expandable member 310 can be in an unexpanded configuration (such as Figure 4B 310 has a length of about 4 cm and can expand to a diameter between 1 cm and 4 cm. In other embodiments, the length and expandable diameter of the expandable member 310 can vary depending on the characteristics and size of the target site for tissue treatment. In other examples, the expandable member 310 can be expanded in other suitable ways (e.g., rolling, unfolding, pushing).

[0107] The catheter 300 also includes a flexible substrate 312 that can be coupled to or otherwise supported by the expandable member 310, wherein the flexible substrate 312 can surround at least a portion of the expandable member 310. In some embodiments, the flexible substrate 312 can be a thin layer or sheet comprising an electrically insulating polymer material such as a polyimide, polyester, or other suitable thermoplastic or thermosetting polymer film. In other embodiments, the flexible substrate 312 can include a polymer-covered material. Figure 5-Figure 6 Additional details of various components, features, and embodiments of flexible substrate 312 are provided.

[0108] The catheter 300 includes an electrode array 314 deposited on or otherwise supported by a flexible substrate 312, wherein the electrode array 314 is adapted to provide one or both of electrolysis and electroporation to the target tissue in a manner similar to that described above. Therefore, the electrode array 314 can adopt any suitable configuration that can be operated to generate an electric field. For example, in one embodiment, the electrode array 314 can include a plurality of metal traces deposited on the flexible substrate 312. The metal traces can include any suitable conductive material, such as gold, copper, stainless steel, titanium, graphene, graphite, etc. In general, the electrode material can be selected so that the electrode material does not actively participate in the electrolysis product and / or leave material residues. In some embodiments, the electrode material can be selected to minimize ion transfer from the electrode material to the target tissue. For example, steel may be less preferred. Titanium and gold may have a certain degree of participation in the electrolysis process, but they may not produce toxic residues and can be used in some examples.

[0109] In general, the electrodes used in the example configurations described herein (particularly with reference to Figure 5-16DThe electrodes described herein are arranged in a bipolar configuration. Typically, in a bipolar configuration, current can travel from one electrode in a pair of electrodes to the other electrode in the pair of electrodes. Therefore, the electrodes in the pair can be considered to be of opposite polarity. In some configurations, multiple pairs of electrodes can be used, with current passing through each pair of electrodes. Any shape of electrodes can be used in the example configurations described herein, including circular, square, rectangular or other shapes. Interdigitated electrodes can also be used.

[0110] In other examples, the electrode can be arranged in a monopolar configuration, or can be arranged in a combination of bipolar and monopolar configurations. The monopolar configuration can include an active electrode (e.g., an electrode on, in, or near the target tissue) and a return electrode. In some examples, the return electrode can be placed away from the target tissue but in contact with the patient (e.g., using a pad with an electrode). In this way, a polarity (e.g., the polarity of the active electrode) is in contact with or close to the target tissue. Therefore, the monopolar configuration of the electrode can include a pair of electrodes, one of which is excited, and an electrode is used as a return. The return electrode may not be provided on a device identical to the excited electrode or a separate device. For example, the return electrode may be provided on a pad placed near the tissue. In the monopolar configuration, multiple active electrodes may be present, and in some examples, current may be passed through a shared return electrode, or in other examples, current may be passed through a corresponding return electrode.

[0111] like Figure 4B As shown, the catheter 300 includes wiring 316 that runs along the elongated member 302 to provide electrical signals such as voltage and / or current to the electrode array 314. In one embodiment, the wiring 316 can run down the length of the elongated member 302 to the controller 14 and / or power source 12 (see FIG. Figure 1 ). In other embodiments, other suitable wiring configurations may be used to power the electrode array 314.

[0112] Overall reference Figure 1-4B, a brief overview of an example delivery of a catheter 300 to the duodenum for ablating a mucosal lining according to an example embodiment is provided below. In one example, a medical device system 200 (e.g., an endoscope) can be delivered to the duodenum in a transoral manner, which includes entering through the patient's esophagus, navigating through the stomach, and ultimately entering the duodenum for disposal. With the medical device system 200 in place, the catheter 300 is navigated through the working channel 221 and into position within the duodenum. Thereafter, the expandable member 310 is inflated to radially expand the expandable member 310 to a target diameter. The expansion of the expandable member 310 applies a radial force to the flexible substrate 312, which causes the flexible substrate 312 to expand and / or expand toward the mucosal lining of the duodenum. When the flexible substrate 312 is deployed, the electrode array 314 on the flexible substrate 312 moves to a position adjacent to (or in contact with) the mucosal lining. The expansion of the expandable member 310 and / or the flexible substrate 312 can be controlled to ensure that the electrode array 314 is properly contacted (or otherwise positioned close enough) to treat the mucosal lining while avoiding over-expansion. With the electrode array 314 in place, the current travels through the wiring 316 and reaches the electrode array 314 to generate an electric field for electroporation and / or electrolysis. Preferably, the area to be ablated is located in the area around the expandable member 310, and the goal of the electric field is to ablate the mucosal lining of the duodenum without affecting adjacent tissue. After treatment is completed, the expandable member 310 is deflated to retract the flexible substrate 312 and the electrode array 314 and move them away from the tissue and back to the stowed position to facilitate removal of the catheter 300.

[0113] In some embodiments, the catheter 300 and other catheters described herein can be actuated by a robot-assisted manipulator system (e.g., manipulator assembly 102). The catheter may include or be coupled to a drive unit (e.g., drive unit 204) having one or more drive inputs that are removably coupled to a drive element (e.g., actuator) of the manipulator assembly and receive power therefrom. The drive input of the catheter may be coupled to the drive output of the manipulator assembly. In addition, the drive input of the catheter may be coupled to the distal portion of the catheter via one or more actuation drive members (e.g., actuation cables, actuation rods, tension members, etc.) to perform actions such as advancing, retracting or articulating the distal end of the catheter and the expansion and / or retraction of the expandable member described herein to adjust the flexible substrate between the deployment position and the stowed position. In some embodiments, the shaft of the elongated member may be coupled to the drive unit to advance and retract the shaft. In addition, the drive unit may be coupled to a controller (e.g., controller 14) and / or a power supply (e.g., power supply 12) to provide electrical power to the electrodes on the flexible substrate. The drive unit can be electrically coupled to the flexible substrate via one or more cables that travel along or through the axis of the catheter. In alternative embodiments, the controller and power supply can provide power to the cables without being coupled to the drive unit (e.g., the controller and power supply can be independent of the drive unit).

[0114] As previously described, in some embodiments, the catheter 300 can be repositioned (e.g., advanced or retracted relative to the medical device system 200) to a different area of ​​the duodenum, and the process repeated as needed to sequentially treat larger areas of the mucosal lining. It should be understood that while the above examples illustrate the use of a delivery system including an endoscope to deliver the catheter to the treatment area, other delivery systems may be used in addition or alternatively in other embodiments. In other embodiments, the catheter 300 can be delivered by itself without the assistance of an endoscope or other delivery system. In addition, it should be understood that treatment in the duodenum is an example of catheter 300 delivery, and the catheter 300 can be used for other target tissues.

[0115] Figure 5 Another catheter 500 is illustrated having a flexible substrate 502 and an electrode array 520 for delivery to a target tissue area according to an example embodiment. Figure 6 A flexible substrate 502 of a catheter 500 is shown according to an example embodiment. Figure 4A and Figure 4B The catheter 500 is arranged in a similar manner to the catheter 300. Therefore, the following description of the catheter 500 may not provide additional details of various similar components to avoid repetition, wherein it should be understood that these components can have the same or substantially similar features as the corresponding components of the catheter 300.

[0116] Specific reference Figure 6 , the flexible substrate 502 includes a base 504 having a top surface 506 and an opposite bottom surface (not shown). The base 504 can be a thin layer or sheet including an electrically insulating polymer material (e.g., a polyimide, polyester, or other suitable thermoplastic or thermosetting polymer film), or can include a base material having one or more coatings including a suitable electrically insulating polymer. The base 504 includes a head or distal portion 508, an opposite foot or proximal portion 510, a first peripheral side portion 512, and a second peripheral side portion 514. The peripheral side portions 512, 514 each span between the head portion 508 and the foot portion 510 along opposite ends of the base 504.

[0117] The base 504 of the flexible substrate 502 also includes a first arm segment 516 extending outward from the head portion 508 and a second arm segment 518 extending outward from the foot portion 510. The arm segments 516, 518 can each extend substantially perpendicular to the respective head portion 508 and foot portion 510. In some embodiments, the arm segments 516, 518 are aligned relative to each other along a first axis A that extends across the flexible substrate 502 and traverses both the head portion 508 and the foot portion 510. For example, the arm segments 516, 518 can be aligned relative to each other along the second peripheral side portion 514 of the flexible substrate 502. This configuration provides the flexible substrate 502 with a plurality of peripheral portions, such as the first peripheral portion 514 of the flexible substrate 502. Figure 6 The arm segments 516, 518 may alternatively be aligned along the first peripheral side portion 512. In other embodiments, one of the arm segments 516, 518 may extend from the head portion 508 and the other of the arm segments 516, 518 may extend from the foot portion 510, but are not aligned relative to each other. In other words, the arm segments 516, 518 are not aligned along a common axis extending from the head portion 508 and the foot portion 510 across the flexible substrate 502. In some embodiments, the arm segments 516, 518 are each formed as an integral part of the flexible substrate 502, but one or both of the arm segments 516, 518 may also be formed as a separate component from the flexible substrate 502 that can be coupled in a similar configuration as described above (e.g., via an adhesive or other suitable bonding mechanism).

[0118] The flexible substrate 502 includes an electrode array 520 disposed along a top surface 506 of the base 504. As previously described, the electrode array 520 may be in any suitable configuration operable to generate an electric field to provide electroporation and / or electrolysis for tissue treatment. Figure 6In an embodiment, the electrode array 520 includes a plurality of metal traces 522, 524 deposited on the flexible substrate 502, wherein the metal traces 522, 524 include any suitable conductive material, such as gold, copper, stainless steel, titanium, graphene, graphite, etc. In an embodiment, at least a portion of the electrode array 520 extends to one of the arm segments ( Figure 6 518 in the arm segment, wherein another arm segment ( Figure 6 The arm segment 516 in the embodiment of the present invention is substantially free of the electrode array 520. In other embodiments, the electrode array 520 may extend to both arm segments 516, 518, or may not extend to both arm segments 516, 518.

[0119] The base 504 of the flexible substrate 502 may also optionally include a plurality of holes 526 formed therein to provide additional flexibility to the flexible substrate 502 (and the overall design of the catheter 500) to facilitate alignment with the reference Figure 2-3B In some embodiments, at least some of the holes 526 are disposed between portions of the electrode array 520 to avoid or minimize the effect on the ability to generate the desired electric field for treatment purposes. For example, referring to Figure 6 , the electrode array 520 may include a first trace element 522 and a second trace element 524 offset from each other along the top surface 506 of the base 504. In such an embodiment, at least some holes 526 are disposed between the trace elements 522, 524 on the flexible substrate 502. In other embodiments, the holes 526 may be arranged differently to provide the flexible substrate 502 with the desired flexibility to navigate tortuous structures within the body. In other embodiments, the holes 526 may be omitted.

[0120] The flexible substrate 502 may include any suitable size to achieve the purposes described herein. For example, in one embodiment, the base 504 may have a length from the first peripheral side portion 512 to the second peripheral side portion 514 ranging between 60-180 mm. The base 504 may have a width from the head portion 508 to the foot portion 510 (excluding the arm segments 516, 518) ranging between 7-60 mm. The arm segments 516, 518 may each range from 2-45 mm (measured from the corresponding head portion 508 and foot portion 510). The base 504 may have a thickness ranging between 12-254 μm, and the electrode array 520 may have a thickness ranging between 12-102 μm.

[0121] refer to Figure 5 and Figure 6 , the following describes an example coupling arrangement of the flexible substrate 502 and the expandable member 534 according to one embodiment. Briefly, referring to Figure 5, the catheter 500 includes an elongated member 528 having a distal portion 530 and a proximal portion (not shown). In some embodiments, the distal portion 530 may include a distal tip 532 designed to help guide the catheter 500 to a target tissue region. The catheter 500 also includes an expandable member 534 (e.g., an inflatable balloon, a mesh, or other suitable expandable member) coupled to the elongated member 528. The expandable member 534 can be coupled to the elongated member 528 between its distal portion 530 and proximal portion, wherein the expandable member 534 can be radially expandable relative to the elongated member 528, as previously described with reference to the catheter 300.

[0122] The flexible substrate 502 is coupled to the expandable member 534 and may be expanded or otherwise deployed in a manner similar to that previously described. Figure 5 , when the flexible substrate 502 is in the stowed position, the flexible substrate 502 tightly surrounds at least a portion of the expandable member 534. In some embodiments, the flexible substrate 502 can be wrapped around the expandable member 534, wherein the segments of the flexible substrate 502 overlap on other segments of the flexible substrate 502. When in the stowed position against the expandable member 534, the flexible substrate 502 can have an outer diameter in the range of 5-20 mm. When in the stowed position, the outer diameter is preferably kept as small as possible to facilitate the delivery and retraction of the catheter 500 during and after treatment. For example, the outer diameter in the stowed configuration can be sized to fit within the working channel 221 of the medical device system 200 (e.g., endoscope). Once expanded, in some embodiments, the flexible substrate 502 can have an outer diameter in the range of 6-50 mm, and in some embodiments, can have an outer diameter in the range of 20-50 mm. In some embodiments, the outer diameter can be based on the tissue contour being treated and / or the expansion specifications of the expandable member 534.

[0123] In some embodiments, the flexible substrate 502 can be processed to enable the flexible substrate 502 to properly expand under pressure (e.g., when the expandable member 534 is expanded), and to ensure that the flexible substrate 502 returns to its collapsed state (e.g., stowed configuration) after the pressure source is removed (e.g., when the expandable member 534 is deflated). For example, in one embodiment, the flexible substrate 502 can undergo a shaping process using heat and pressure to become a coiled configuration by approaching the glass transition temperature of the material constituting the flexible substrate 502. The flexible substrate 502 can also be cooled under pressure to maintain shape memory in the coiled configuration. Initially forming the flexible substrate 502 into a coiled configuration causes the flexible substrate 502 to return to the coiled configuration after deployment to facilitate retraction.

[0124] In some embodiments, certain aspects of the flexible substrate 502 may also be manipulated as desired to promote specific characteristics. For example, the flexible substrate 502 may have a tail portion 536 formed along the outer end of the flexible substrate 502 (e.g., along the peripheral side portion 512) after the flexible substrate 502 is wrapped around the expandable member 534 as previously described (see Figure 5 ). Depending on the material composition and / or other characteristics of the flexible substrate 502, the tail portion 536 may tend to curl inwardly against the expandable member 534 when in the stowed configuration and / or may cause the flexible substrate 502 to partially or completely unfold. Therefore, in one embodiment, after the flexible substrate 502 is formed into a rolled configuration as previously described, the tail portion 536 may be heated to straighten the tail portion 536. In some embodiments, the straightened tail portion 536 may also help prevent the flexible substrate 502 from winding into multiple barrels (e.g., one barrel around the expandable member 534 and a second barrel adjacent to the expandable member 534). If over-expanded during the deployment phase, the flexible substrate 502 may tend to wind into multiple barrels.

[0125] In other embodiments, other shaping techniques may be applied to the flexible substrate 502 to ensure that it maintains its shape about the expandable member 534 during delivery in the stowed configuration, during deployment in the expanded configuration, and during retraction to the stowed configuration for removal after treatment.

[0126] When the flexible substrate 502 is in the wrapped and stowed configuration, one arm segment ( Figure 5 The first arm segment 516 in the embodiment of the present invention extends outward from the flexible substrate 502 and toward the distal portion 530 of the slender member 528. The first arm segment 516 is coupled to the expandable member 534 to hold the flexible substrate 502 in place against the expandable member 534 in the stowed position. In some embodiments, the first arm segment 516 can also (or alternatively) be coupled to the distal tip 532. When the flexible substrate 502 encounters resistance during catheter delivery, positioning, or retraction, the first arm segment 516 helps prevent the flexible substrate 502 from peeling off or away from the expandable member 534 in the proximal direction. The first arm segment 516 can be coupled to the expandable member 534 (and / or the distal tip 532) using any suitable technique (e.g., a bonding agent or a suitable adhesive). In some embodiments, after the expandable member 534 is expanded to deploy the flexible substrate 502, the first arm segment 516 remains coupled to the expandable member 534. In other embodiments, during the deployment of the flexible substrate 502, the first arm segment 516 can be removed from the expandable member 534. As shown in FIG. Figure 5As shown, catheter 500 includes one or more wires 538 coupled to electrode array 520 along a proximal portion of flexible substrate 502, wherein wires 538 travel toward a proximal portion of elongated member 528 and are coupled to a power source (e.g., Figure 1 A power source 12). A wire 538 can be coupled to the flexible substrate 502 along the second arm segment 518 to help hold the flexible substrate 502 in place against the expandable member 534 along the proximal portion of the elongated member 528 during catheter delivery and retraction.

[0127] In some embodiments, as previously described, the first arm segment 516 of the flexible substrate 502 coupled along the distal portion 530 is substantially free of any electrodes of the electrode array 520, as it primarily serves as a support tie to hold the flexible substrate 502 in place, while the second arm segment 518 may include portions of the electrode array 520 for coupling to the wires 538 to generate an electric field for treatment. It should be understood that while the embodiments illustrate and describe the first arm segment 516 coupled along the distal portion 530 of the elongated member 528 and the second arm segment 518 coupled along the proximal portion of the elongated member 528, in other embodiments, the positioning of the arm segments 516, 518 may be swapped.

[0128] In some embodiments, the head portion 508 and the foot portion 510 of the flexible substrate 502 can form relatively stiff, sharp, and / or rigid leading and trailing edges that can rub or otherwise interfere with tissue when the flexible substrate 502 is in the stowed configuration during delivery and / or retraction of the catheter 500. As a result, the edges can inadvertently damage tissue surrounding the treatment site. Figure 7A to Figure 10 , the following disclosure provides various potential solutions for minimizing trauma during catheter delivery and retraction.

[0129] Fig. 7A Another embodiment of a flexible substrate 700 that can be used with the catheters 300, 500 described above according to example embodiments is illustrated. In general, the flexible substrate 700 includes a base 702 having a top surface 704 and an opposite bottom surface (not shown). The base 702 can be formed in a manner similar to that of the embodiment of the present invention. Figure 6 The base 702 of the flexible substrate 502 includes an electrically insulating polymer material (such as polyimide, polyester or other suitable thermoplastic or thermosetting polymer film) in a similar manner. The base 702 includes a head portion (e.g., distal portion) 706, an opposite foot portion (e.g., proximal portion) 708, a first peripheral side portion 710 and a second peripheral side portion 712. The peripheral side portions 710, 712 are both spanned between the head portion 706 and the foot portion 708 along opposite ends of the base 702. The base 702 also includes an electrode array 714 on the top surface 704.

[0130] In one embodiment, the base 702 of the flexible substrate 700 may include a protective coating 716 covering the outer edge surfaces of the head portion 706 and the foot portion 708 and / or the outer edge surfaces of the corresponding peripheral side portions 710, 712. In some embodiments, the protective coating 716 may extend over a portion of the top surface 704 and the opposite bottom surface, and may also extend beyond the corresponding outer edge surfaces of the base 702 of the flexible substrate 700. The protective coating 716 may be any suitable material, such as silicone or other soft polymers, and may have any suitable thickness as needed to provide an atraumatic surface to the peripheral side portions 710, 712 (as well as the head portion 706 and the foot portion 708) of the flexible substrate 700, as described below with reference to Figure 8 Detailed description. For example, in one embodiment, the protective coating 716 may be 1 mm thick, or may range in thickness from 0.25 mm to 2 mm, or may have other suitable dimensions. The protective coating 716 may be applied or deposited onto the flexible substrate 700 in any suitable manner. For example, in one embodiment, the protective coating 716 may be overmolded onto the flexible substrate 700 as part of a post-processing procedure. In some embodiments, a nanospray coating (or other suitable coating) may be applied to reduce friction of the flexible substrate 700.

[0131] In some embodiments, a protective coating 716 (or a different protective coating not shown) can cover some or all of the top surface 704 and / or bottom surface of the flexible substrate 700 to further prevent potential tissue damage from any aspect of the flexible substrate 700. The protective coating 716 can also cover some or all of the electrode array 714 disposed on the top surface 704 of the flexible substrate 700. In these embodiments, the protective coating 716 can include silicone, parylene, or other suitable coatings. In the case where the electrode array 714 is under-deployed, both silicone and parylene can be used as suitable insulators to minimize potential complexity. In some embodiments, the internal lubricity created by the protective coating 716 can promote smooth deployment and unfolding of the flexible substrate 700, because it can be used to reduce friction between overlapping sections of the flexible substrate 700, especially in the case where the material constituting the flexible substrate 700 may be somewhat sticky or tacky. In addition, the protective coating 716 can also help prevent the electrode array 714 from adhering to the tissue and / or itself when it is retracted from the deployed configuration to the rolled-up stowed configuration for removal. In some embodiments, additional sprays or other substances may be applied to the flexible substrate 700 as needed to reduce friction, thereby ensuring that the flexible substrate 700 is deployed as desired.

[0132] Figure 8 FIG. 1 is a diagram illustrating a method for Fig. 7A The present invention provides an example catheter 800 for use with the flexible substrate 700 of the embodiment. The catheter 800 may have the same or substantially similar features and similar functions as previously described with respect to the catheters 300, 500. Therefore, additional details of the catheter 800 may not be described in further detail below to avoid repetition and / or obscuring the more relevant details of this embodiment. With particular reference to Figure 8 , when the flexible substrate 700 is coupled to the expandable member 802, the head portion 706 and the foot portion 708 form the front (e.g., distal) edge and the rear (e.g., proximal) edge of the flexible substrate 700, respectively, which can be relatively hardened, sharp and / or rigid. In this configuration, the flexible substrate 700 may cause accidental damage to the tissue during catheter delivery and disposal, as previously described. By coating the head portion 706 and the foot portion 708 (or at least coating the head portion 706 that forms the front edge of the flexible substrate 700 during catheter delivery) with a protective coating 716 as described above, the risk of traumatic injury is reduced because the front edge and / or the rear edge are coated with a soft material relative to the material constituting the flexible substrate 700.

[0133] As referenced above Fig. 7A and Figure 8 As described, in some embodiments, some or all of the outer edge surfaces of the flexible substrate 700 may be covered with a protective coating 716 to reduce potential trauma to surrounding tissue when the flexible substrate 700 is in a stowed configuration during catheter delivery. However, in some embodiments, the protective coating 716 around the edges of the flexible substrate 700 increases the overall thickness of the flexible substrate 700 when in the stowed configuration because the protective coating 716 stacks on itself when the flexible substrate 700 is wrapped around the expandable member 802. This stacking effect may also affect how tightly the flexible substrate 700 can be wrapped around the expandable member 802 when in the stowed configuration. In some embodiments, the thickness of the protective coating 716 may create a raised portion of the flexible substrate 700 and may reduce the opening force of the flexible substrate 700 due to the capstan effect. Therefore, in some embodiments, the design of the head portion and the foot portion of the flexible substrate 700 may be altered to minimize the stacking of the protective coating 716, as described below with reference to Figure 7B As described.

[0134] Figure 7B Another embodiment of a flexible substrate 750 that can be used with any of the catheters 300, 500, 800 described above (or with other suitable catheter designs) according to example embodiments is illustrated. In general, the flexible substrate 750 includes a number of components similar to those of the reference Fig. 7A For example, referring to the flexible substrate 700 Figure 7B, the flexible substrate 750 includes a base 752 having a top surface 754 and an opposite bottom surface (not shown). The base 752 can be formed with Fig. 7A The base 702 of the flexible substrate 700 includes an electrically insulating polymer material (such as polyimide, polyester or other suitable thermoplastic or thermosetting polymer film) in a similar manner. The base 752 includes a head portion (e.g., distal portion) 756, an opposite foot portion (e.g., proximal portion) 758, a first peripheral side portion 760, and a second peripheral side portion 762. The peripheral side portions 760, 762 each span between the head portion 756 and the foot portion 758 along opposite ends of the base 752. The base 752 also includes an electrode array 764 on the top surface 754.

[0135] In one embodiment, the head portion 756 and the foot portion 758 can be tapered, wherein the head portion 756 and the foot portion 758 are angled relative to each other. For example, in one embodiment, the width of the base 752 of the flexible substrate 750 can gradually narrow along the head portion 756 and the foot portion 758 from the second peripheral side portion 762 toward the first peripheral side portion 760. In this configuration, the length of the second peripheral side portion 762 is greater than the corresponding length of the first peripheral side portion 760, as shown in FIG. Figure 7B In this conical configuration, when the flexible substrate 750 surrounds the expandable member (e.g., Figure 8 When the expandable member 802 of the flexible substrate 750 is wound into a collapsed configuration, the tapered head portion 756 and foot portion 758 cause the protective coating 766 to not stack on itself when the flexible substrate 750 is tightly rolled. Instead, when the flexible substrate 750 is wound, the layer of protective coating 766 along the head portion 756 and foot portion 758 is located inside of and does not overlap with the continuous layer.

[0136] Fig. 9 Another embodiment of a catheter 900 having features designed to prevent trauma during catheter delivery and retraction is illustrated. In general, catheter 900 can have the same or substantially similar features as catheters 300, 500. Therefore, certain details of catheter 900 are not described in further detail below to avoid repetition and / or obscuring the more relevant details of this embodiment. Briefly, reference is made to Fig. 9 The catheter 900 includes an elongated member 902, an expandable member (from Fig. 9 ) and a flexible substrate 906 coupled to the expandable member in a similar manner and with similar functionality as previously described with respect to catheters 300, 500.

[0137] refer to Fig. 9 The catheter 900 may include a front edge 910 adjacent to the flexible substrate 906 (which may be similar to the front edge 910 of the flexible substrate 906). Figure 8In a similar manner as described above, a first liner 908 is provided along one of the head portion or foot portion of the flexible substrate 906, wherein the first liner 908 is primarily designed to prevent tissue trauma during delivery of the catheter 900. The first liner 908 can contact the front edge 910 of the flexible substrate 906 to ensure that there is no gap therebetween and to avoid potential capture or entrapment of tissue therein. In some embodiments, the first liner 908 can be positioned near the distal portion 912 of the catheter 900 or between the distal portion 912 and the flexible substrate 906. The first liner 908 can be made of any suitable material, such as an adhesive film material or other soft material, so as to provide a soft interface and shield the front edge 910 of the flexible substrate 906, thereby minimizing contact or interaction of the front edge 910 with tissue primarily during catheter delivery (but also protecting tissue during retraction).

[0138] In some embodiments, the first liner 908 can be coupled to the elongated member 902, the distal tip 914 of the elongated member 902, the expandable member and / or the flexible substrate 906. In some embodiments, the first liner 908 is coupled in such a manner that the first liner 908 remains in place against the catheter 900 during and after the deployment of the flexible substrate 906 for treatment. Thus, the first liner 908 can be made of such a material that is sufficiently flexible so as not to impair the delivery of the catheter 900 or the deployment and retraction of the expandable member and the flexible substrate 906. In other embodiments, the first liner 908 can be a silicone, polyurethane or other suitable polymer coating that is weakly attached to the flexible substrate 906 and is designed to peel off during expansion of the expandable member and the flexible substrate 906. In other embodiments, the first liner 908 can be made as a separate cap designed for subsequent attachment to the catheter 900. In some embodiments, first liner 908 may be a coating designed to keep leading edge 910 low profile until flexible substrate 906 is expanded, where the coating is designed to act like a weak temporary adhesive that easily tears or peels during expansion.

[0139] In some embodiments, the catheter 900 includes a second pad 916 disposed adjacent to a rear edge 918 of the flexible substrate 906 (which may be defined along the other of the head portion or foot portion of the flexible substrate as previously described). The second pad 916 may contact the rear edge 918 of the flexible substrate 906 to ensure that there is no gap therebetween. The second pad 916 may be made of any suitable material (such as an adhesive film material or other soft material) to provide a soft interface and shield the rear edge 918 of the flexible substrate 906 to minimize contact or interaction of the rear edge 910 with tissue primarily during catheter retraction (but also to protect tissue during delivery). The second pad 916 may otherwise be substantially similar to the first pad 908 described above. Therefore, the features and characteristics of the first pad 908 described above may be equally applicable to the second pad 916, but are not discussed in further detail to avoid repetition.

[0140] Fig.10 Another embodiment of a catheter 1000 designed to have features designed to prevent trauma during catheter delivery, positioning, and retraction is illustrated. In general, catheter 1000 can have the same or substantially similar features as catheters 300, 500. Therefore, certain details of catheter 1000 are not described in further detail below to avoid repetition and / or obscuring the more relevant details of this embodiment. Briefly, reference is made to Fig.10 , catheter 1000 includes an elongated member 1002 , an expandable member 1004 coupled thereto, and a flexible substrate 1006 coupled to the expandable member 1004 in a similar manner and with similar functionality as previously described with respect to catheters 300 , 500 .

[0141] refer to Fig.10 , the catheter 1000 may include a first liner 1008 disposed adjacent to a leading edge 1010 of the flexible substrate 1006 (which may be defined along one of the head portion or foot portion of the flexible substrate as previously described), wherein the first liner 1008 is primarily designed to prevent tissue trauma during delivery of the catheter 1000. The first liner 1008 may contact the leading edge 1010 of the flexible substrate 1006 to ensure that there is no gap therebetween. The first liner 1008 may be positioned adjacent to a distal portion 1012 of the catheter 1000 or between the distal portion 1012 and the flexible substrate 1006. Fig.10 As shown, the first pad 1008 can be formed by partially expanding or inflating the expandable member 1004 so that the first pad 1008 fully covers or shields the leading edge 1010 of the flexible substrate 1006, thereby minimizing contact or interaction of the leading edge 1010 with tissue primarily during catheter delivery (but also protecting tissue during retraction).

[0142] In some embodiments, the catheter 1000 may also include a second pad 1014 (shown in an unexpanded configuration) disposed proximate a rear edge 1016 of the flexible substrate 1006 (which may be defined along the other of the head portion or foot portion of the flexible substrate as previously described). The second pad 1014 may contact the rear edge 1016 of the flexible substrate 1006 to ensure that there is no gap therebetween. In a similar manner to the first pad 1008, the second pad 1014 may be formed by partially expanding or inflating the expandable member 1004 such that the second pad 1014 substantially covers or shields the rear edge 1016 of the flexible substrate 1006, thereby minimizing contact or interaction of the rear edge 1016 with tissue primarily during catheter retraction (but also protecting tissue during delivery).

[0143] The pads 1008, 1014 can be made in any suitable manner. For example, in one embodiment, the first tube 1018 can be positioned on the flexible substrate 1006, and the second tube 1020 can be positioned on the distal tip 1022 of the elongated member 1002. The first tube 1018 and the second tube 1020 are offset from each other, leaving a small gap separating the tubes 1018, 1020. Another tube 1024 having a larger diameter than the tubes 1018, 1020 can be positioned in the gap and on the tubes 1018, 1020 to surround the shoulder around the exposed portion of the expandable member 1004. The tubes 1018, 1020, 1024 can be any suitable material, such as tetrafluoroethylene (TFE) and the like. For example, when the tubes 1018, 1020, 1024 are in a position such as Fig.10 In the case of the position shown, the exposed portion of the expandable member 1004 can be heated under pressure to cause it to fill the gap and create the first liner 1008. A similar process can be used to create the second liner 1014 along the rear edge 1016. Once the liner 1008, 1014 has been created, the tubes 1018, 1020, 1024 can be removed to maintain a low overall profile of the catheter 1000 and facilitate delivery of the catheter to and from the target tissue site. In another embodiment, the expandable member 1004 can be preset and / or pre-expanded to form the liner 1008, 1014. In such an embodiment, the expandable member 1004 can include a thermosetting material to facilitate the formation of the liner 1008, 1014 during the manufacturing process.

[0144] In some embodiments, the expandable member 1004 can return to its nominal shape (e.g., the cushions 1008, 1014 can be displaced or removed) after the expandable member 1004 is inflated to deploy the flexible substrate 1006. In other embodiments, the cushions 1008, 1014 can be permanently retained so that the cushions 1008, 1014 are in place against the leading edge 1010 and the trailing edge 1016, respectively, after the expandable member 1004 is deflated and the flexible substrate 1006 is retracted to the stowed position to protect tissue during catheter removal.

[0145] Fig.11A A catheter 1100 is illustrated having an adjustment member 1108 operable to maintain a flexible substrate 1106 in a stowed position during delivery to a target area according to an example described herein. The adjustment member 1108 may additionally be operable to transition the flexible substrate 1106 from an expanded configuration (e.g., from a deployed position or a partially deployed position) to a stowed position for delivery or removal. In general, the catheter 1100 may have the same or substantially similar features as the catheters 300, 500. Accordingly, certain details of the catheter 1100 are not described in further detail below to avoid repetition and / or obscuring the more relevant details of the embodiment. Briefly, reference is made to Fig.11A , catheter 1100 includes an elongated member 1102 , an expandable member 1104 coupled thereto, and a flexible substrate 1106 coupled to the expandable member 1104 in a similar manner and with similar functionality as previously described with respect to catheters 300 , 500 .

[0146] refer to Fig.11A , the catheter 1100 further includes an adjustment member 1108 coupled to one or both of the flexible substrate 1106 and the expandable member 1104, wherein the adjustment member 1108 is adjustable to hold the flexible substrate 1106 in the stowed position against the expandable member 1104. In some embodiments, the adjustment member 1108 is further adjustable to drive the flexible substrate 1106 from the deployed position or the expanded position back to the stowed position to facilitate removal of the catheter 1100. Additional details of the adjustment member 1108 and its function will be described below.

[0147] Fig.11AAn example embodiment is illustrated in which an adjustment member 1108 is directly coupled to the flexible substrate 1106. The adjustment member 1108 may include any suitable member that facilitates applying tension to the flexible substrate 1106 and allows the tension to be controlled as desired via adjustment of the adjustment member 1108. For example, in one embodiment, the adjustment member 1108 may be a tension element, such as a cable or wire that may be formed from one or more fibers (e.g., braided fibers, sutures, Kevlar fibers, etc.). In this embodiment, the tension element is coupled to the flexible substrate 1106 and extends proximally along the length of the elongated member 1102 to the proximal end 1114 of the elongated member 1102. Tension may be applied to the tension element to tighten or maintain the flexible substrate 1106 in a stowed position. The tension may be released from the tension element to allow the flexible substrate 1106 to transition to a deployed or extended position.

[0148] refer to Fig.11A , the flexible substrate 1106 includes a base 1110 having one or more holes 1112 formed thereon. In some embodiments, the holes may include slits, eyelets, openings, or other suitable attachment or anchoring points formed on the base 1110 of the flexible substrate 1106. The adjustment member 1108 may be coupled to the flexible substrate 1106 via at least some of the one or more holes 1112 in any suitable manner. For example, in one embodiment, the adjustment member 1108 may be woven through at least some of the one or more holes 1112 to couple the adjustment member 1108 to the flexible substrate 1106.

[0149] As previously described, the adjustment member 1108 is configured to hold the flexible substrate 1106 in a stowed configuration against the expandable member 1104. In one example, tension can be applied to the adjustment member 1108, such as by pulling the adjustment member 1108 outwardly (or proximally) along the proximal end 1114 of the elongated member 1102, to tighten the adjustment member 1108 against the one or more holes 1112 and hold the flexible substrate 1106 in a compact stowed configuration. In some embodiments, the tension applied to the adjustment member 1108 can adjust the flexible substrate 1106 and pull the flexible substrate 1106 to a tighter coiled configuration against the expandable member 1104. The adjustment member 1108 can be tightened by the operator as needed to reduce the overall profile of the catheter 1100 as needed, such as during key workflow steps. In some embodiments, the adjustment member 1108 can be coupled to the robot-assisted manipulator system 100 (or other suitable system) to provide actuation, control and / or electrical power to the flexible substrate 1106 as needed. Control via the manipulator system can facilitate fine adjustment to provide tighter control of the flexible substrate 1106 as needed. The adjustment member 1108 can be coupled to the flexible substrate 1106 before delivery to the treatment site or at the treatment site as needed and before treatment. In embodiments where the catheter 1100 is actuated by a robotic-assisted manipulator system (e.g., manipulator assembly 102), the catheter 1100 can include or be coupled to a drive unit (e.g., drive unit 204) having one or more drive inputs that are removably coupled to a drive element (e.g., an actuator) of the manipulator assembly as described above and receive power therefrom. The drive input of the catheter 1100 can be coupled to the adjustment member 1108 to actuate the adjustment member 1108. For example, in some embodiments where the adjustment member 1108 includes a tensioning element such as a cable, the cable can be wrapped around one or more capstans coupled to the drive inputs, such that when the capstans are rotated in a first direction (e.g., via actuation of a drive output of the manipulator system), the capstans cause the cables to be retracted to tighten the flexible substrate 1106. When the capstan is rotated in a second direction opposite the first direction, the capstan may cause the cable to pay out to loosen the flexible substrate 1106 and allow the flexible substrate 1106 to expand (eg, via expansion of the expandable member 1004 ).

[0150] In some embodiments, the adjustment member 1108 can also be adjusted to control the movement of the flexible substrate 1106 from the stowed position to the deployed position after the initial adjustment, thereby maintaining the flexible substrate 1106 in the stowed position. For example, the adjustment member 1108 can be initially tightened to maintain the flexible substrate 1106 in a compact stowed configuration as described above. Thereafter, the adjustment member 1108 can be released to release the tension on the flexible substrate 1106 and facilitate the movement of the flexible substrate 1106 from the stowed position to the deployed position, such as in response to the radial expansion of the expandable member 1104 in a similar manner as previously described. In some embodiments, the adjustment member 1108 can thereafter be tensioned or otherwise tightened after deployment to guide or drive the flexible substrate 1106 back from the deployed configuration to the stowed configuration to prepare the catheter 1100 for removal.

[0151] In other embodiments, the tension of the adjustment member 1108 can be released by cutting the adjustment member 1108 to facilitate adjustment of the flexible substrate 1106. For example, the adjustment member 1108 can be designed to form a continuous loop that can be cut near the proximal portion 1114 of the elongated member 1102 to release the tension on the flexible substrate 1106. In other embodiments, the adjustment member 1108 can be cut near the flexible substrate 1106, such as via a cutting instrument (not shown) that can be introduced in any suitable manner, such as through a working channel of an endoscope. After the adjustment member 1108 is cut, it can be removed from the flexible substrate 1106 to facilitate the desired expansion of the flexible substrate 1106.

[0152] In some embodiments, one or more holes 1112 may be arranged in a particular pattern (such as Fig.11A The zigzag pattern shown in FIG. 1104 is arranged to provide additional control characteristics of the flexible substrate 1106. For example, the common reference Fig.11A and Fig.12 , the adjustment member 1108 can be woven or otherwise coupled to the one or more holes 1112, wherein the adjustment member 1108 contacts the flexible substrate 1106 at certain radial locations (see Fig.121106) to constrain or limit the expansion of the flexible substrate 1106 beyond a predetermined outer diameter. When the adjustment member 1108 is held in place and / or tightened, the flexible substrate 1106 is locked to expand to a maximum diameter equal to the predetermined outer diameter. Once the predetermined outer diameter is reached, the adjustment member 1108 limits further expansion beyond this point. In some embodiments, the target diameter can be adjusted by tightening or loosening the tension on the adjustment member 1108 as needed. Limiting the target diameter to a predetermined threshold can help ensure that the flexible substrate 1106 is expanded to the extent required for effective tissue treatment, but prevents over-extension of the flexible substrate 1106 to help avoid potential problems of retracting the flexible substrate 1106 for removal when the treatment is completed. In some embodiments, after the flexible substrate 1106 is deployed and the treatment is completed, the adjustment member 1108 can be tightened to control the retraction of the flexible substrate 1106 and drive the flexible substrate 1106 back from the expanded deployment position to a compact stowed position against the expandable member 1104 for easy catheter removal.

[0153] In the above example, the adjustment member 1108 is coupled to the flexible substrate 1106 and is operable to hold and / or otherwise control the flexible substrate 1106 relative to the expandable member 1104. In other embodiments, as previously described, the adjustment member 1108 can alternatively or additionally be coupled to the expandable member 1104, wherein the adjustment member 1108 adjusts the expandable member 1104 to hold the flexible substrate 1106 in a stowed position against the expandable member 1104 and / or otherwise achieve the same or similar purposes as described above. For example, in some embodiments, the adjustment member 1108 is coupled to the expandable member 1104, and the adjustment member 1108 is configured to move the expandable member 1104 from an expanded position to a stowed position. Figure 11B-Figure 11C An example embodiment is depicted in which an adjustment member 1108 in the form of a tension element is coupled to an expandable member 1104, which may be an inflatable balloon member.

[0154] Fig. 11B A schematic cross-section of a tension element or adjustment member 1108 coupled to an expandable member 1104 is depicted. Fig. 11B104, an adjustment member 1108 is coupled to a channel 1103 of an expandable member 1104, wherein the channel 1103 is separate from an expansion chamber 1101 of the expandable member 1104. The adjustment member 1108 can be coupled to the channel 1103 by an adhesive, a binder, a press-fit connection, a fastener, etc. In some embodiments, the adjustment member 1108 is coupled to the channel 1103 by being embedded into the channel 1103 during molding. The channel 1103 can be integrally formed with the expandable member 1104, or can be attached to the expandable member 1104 (e.g., by an adhesive, a binder, a fastener, etc.). The expansion chamber 1101 is configured to receive a fluid (such as air or another gas, a liquid such as saline, etc.) for expanding the expandable member 1104, and release the fluid from the expansion chamber 1101 to deflate the expandable member 1104. When fluid is removed from the expansion chamber 1101, tension can be applied to the adjustment member 1108 to move the expandable member 1104 to the stowed position, and / or tension can be applied to the adjustment member 1104 to maintain the expandable member 1104 in the stowed position. A flexible substrate (not shown) surrounds and is coupled to the expandable member 1104 so that the flexible substrate remains tightly wound when the expandable member 1104 is maintained in the stowed position. The tension can be released from the adjustment member 1108 to allow the expansion chamber 1101 to expand when fluid is received in the expansion chamber 1101, and thereby expand the flexible substrate. Fig. 11B In the figure, the channel 1103 for adjusting the member 1108 extends to the outside of the expanded outer diameter of the expandable member 1104. Fig. 11C Another schematic cross-section of a tension element adjustment member 1108 coupled to an expandable member 1104 is depicted. Fig. 11C 1 , a channel 1103' for an adjustment member 1108 is embedded in the wall of the expandable member 1104. For example, the channel 1103' is recessed relative to the expanded outer diameter of the expandable member 1104. During molding of the expandable member 1104, the channel 1103' can be formed, and the adjustment member 1108 can be embedded in the channel 1103'.

[0155] Fig.11D A flexible substrate 1120 according to another example embodiment is illustrated. To avoid obscuring the more relevant aspects of this embodiment, Fig.11D A separate flexible substrate 1120 is schematically illustrated, but it should be understood that the flexible substrate 1120 may be used in the same manner as in previous embodiments (such as Figure 5 , Figure 8-Figure 10 and Fig.11A ) is coupled to an expandable member (not shown) for use with a delivery catheter in a similar manner as described in ). Therefore, the features described herein related to the flexible substrate 1120 can be combined with the catheters or other similar medical devices described in the previous embodiments. Fig.11D, the flexible substrate 1120 includes an adjustment member 1122 that is coupled to the flexible substrate 1120 and is configured to hold the flexible substrate 1120 against the expandable member in a rolled-up configuration. As shown, when the flexible substrate 1120 is in the rolled-up configuration, the various layers of the flexible substrate 1120 overlap or stack one another. For example, in one example configuration, the flexible substrate 1120 may include a first layer 1124 (e.g., Fig.11D 1124), a second layer 1126 below the first layer 1124, a third layer 1128 below the second layer 1126, and so on. It should be understood that the flexible substrate 1120 can include any suitable number of layers that may depend on various factors, such as the overall length of the flexible substrate 1120 and / or the expanded diameter of the expandable member.

[0156] In one embodiment, the alignment member 1122 is configured to couple two or more layers of the flexible substrate 1120. For example, the alignment member 1122 can couple together the first layer 1124 and the second layer 1126. When coupled to the layers 1124, 1126, the alignment member 1122 prevents the flexible substrate 1120 from unfolding or unrolling, which may otherwise occur when the flexible substrate 1120 encounters resistance or other forces acting on the first layer 1124 during catheter delivery.

[0157] In one example, the adjustment member 1122 can have a generally C-shaped profile including an elongated body segment 1130 having a first coupling portion 1132 and a second coupling portion 1134 disposed on respective end portions of the elongated body segment 1130. In one configuration, the elongated body segment 1130 is positioned such that it extends in the axial direction of the flexible substrate 1120 and abuts against an inner portion of the layer being coupled. For example, as shown, the elongated body segment 1130 can be positioned adjacent to the innermost or bottommost layer being coupled (e.g., Fig.11D The coupling portions 1132, 1134 may each include a first segment 1136, 1138 extending from the elongated body segment 1130 and a second segment 1140, 1142 extending from the respective first segment 1136, 1138. In one configuration, the first segments 1136, 1138 may be substantially orthogonal to the elongated body segment 1130, and the second segments 1140, 1142 may be substantially orthogonal to the first segments 1136, 1138 (and substantially parallel to the elongated body segment 1130). Fig.11DAs shown, the first segments 1136, 1138 are used to support the end portions of the capture layers 1124, 1126 of the flexible substrate 1120 to limit lateral movement of the flexible substrate 1120 in the axial direction, and the second segments 1140, 1142 help prevent the flexible substrate 1120 from unfolding or unraveling in the radial direction. In some embodiments, the adjustment member 1122 can be adhered to or otherwise coupled to the outermost layer (e.g., the first layer 1126) of the flexible substrate 1120 to ensure that the adjustment member 1122 is held in place against the flexible substrate 1120. For example, the second segments 1140, 1142 of the adjustment member 1122 can be adhered to the first layer 1126 of the flexible substrate 1120 (e.g., via epoxy, adhesive, mechanical fasteners, etc.). In an alternative arrangement, the elongated body segment 1130 can be positioned adjacent to the outermost layer (e.g., first layer 1124) of the coupled flexible substrate 1120, with the first coupling portion 1132 and the second coupling portion 1134 adhered or otherwise coupled to the innermost layer (e.g., second layer 1126) of the coupled.

[0158] In one example embodiment, the adjustment member 1122 can be modified to essentially replace the continuous elongated body segment 1130 with two smaller segments (not shown), such that the adjustment member 1122 includes a plurality of spaced-apart individual adjustment members, for example, in the shape of two C-shaped hooks located on opposite ends of the flexible substrate (e.g., one on the proximal end of the flexible substrate 1120 and one on the distal end of the flexible substrate 1120). In this arrangement, the first coupling portion 1132 includes segments 1136, 1140 and a first elongated body segment (e.g., a proximal portion of the segment 1130). Similarly, the second coupling portion 1134 includes segments 1138, 1142 and a second elongated body segment (e.g., a distal portion of the segment 1130), wherein the first elongated body segment is spaced apart from the second elongated body segment.

[0159] Further references Fig.11DIn some embodiments where the elongated body segment 1130 is to be positioned between the layers of the rolled flexible substrate 1120, the alignment member 1122 is coupled to the flexible substrate 1120 by inserting the alignment member 1122 between the layers of the rolled flexible substrate 1120 so that the elongated body segment 1130 is adjacent to the lower layer of the flexible substrate 1120 to be captured and with the first coupling portion 1132 and the second coupling portion 1134 extending beyond the end portion of the lower layer of the flexible substrate 1120. Next, the first segments 1136, 1138 are bent away from the elongated body segment 1130 and toward the outer layer of the flexible substrate 1120 to be captured by the alignment member 1122. Next, the second segments 1140, 1142 are bent into contact with the outer layer of the flexible substrate 1120 and bonded to the flexible substrate. In an alternative embodiment, the alignment member 1122 is coupled to the flexible substrate 1120 before the flexible substrate 1120 is placed in the rolled configuration. For example, the second coupling portions 1132, 1134 of the adjustment member 1122 can first be bonded to the portion of the flat flexible substrate 1120 that forms the outermost layer when rolled. The elongated body segment 1130 can then be positioned between the rolled layers during the rolling of the flexible substrate 1120. In embodiments where the elongated body segment 1130 is positioned adjacent to the outermost layer of the flexible substrate 1120, similar assembly steps occur, but where the coupling portions 1132, 1134 are bonded to the inner layers of the flexible substrate 1120.

[0160] Fig.11E Another example of an adjustment member 1150 is shown, which is configured to be used in the same manner as in the above reference Fig.11D The flexible substrate 1152 is held in a similar manner as described above. In the illustrated example, the adjustment member 1150 is designed so that it forms a continuous loop around the capture layer of the flexible substrate 1152. The adjustment member 1150 includes a first elongated segment 1154, a second elongated segment 1156, and a third segment 1158 and a fourth segment 1160 spanning between opposite ends of the elongated segments 1154, 1156. Fig.11E In one example configuration, the second elongated segment 1156 extends in the axial direction of the flexible substrate 1152 and abuts against an inner portion of the bottommost capture layer (e.g., the second layer 1162) of the flexible substrate 1152. Similarly, the first elongated segment 1154 extends in the axial direction and abuts against the outermost layer (e.g., the first layer 1164) of the flexible substrate 1152. The elongated segments 1154, 1156, together with the third segment 1158 and the fourth segment 1160, are similar to those described above with reference to Fig.11DThe flexible base 1152 is constrained in a rolled, stowed configuration against an expansion member (not shown) in a similar manner as described. In some examples, the adjustment member 1150 can be adhered to or otherwise coupled to the outermost capture layer (e.g., first layer 1164) of the flexible substrate 1152. In other examples, the adjustment member 1150 may not be adhered to or directly coupled to any layer of the flexible substrate 1152.

[0161] As mentioned above, Fig.11D and Fig.11E Example embodiments are provided for retaining the flexible substrate 1120, 1152 in a coiled, stowed configuration against an expandable member (not shown), wherein the adjustment member 1122, 1150 helps prevent the flexible substrate 1120, 1152 from unfolding or unrolling during catheter delivery in response to resistance or other forces acting on the flexible substrate 1120, 1152. In alternative embodiments, the flexible substrate may alternatively include a flexible substrate 1120, 1152 that is adapted to be in contact with the flexible substrate 1120, 1152. Figure 5 In this configuration, the one or more segments of the flexible substrate may be tucked under the rolled flexible substrate and abut against the outermost layer of the flexible substrate (e.g., in a manner similar to the segments 516 of the flexible substrate 502). Fig.11D The segments 1140, 1142 are coupled (such as by an adhesive or in another suitable manner) to maintain the flexible substrate in the collapsed configuration.

[0162] Fig.11F Another example of a flexible substrate 1180 is illustrated that includes one or more adjustment members 1194 (illustrated as arm segments) along edge portions of the flexible substrate 1180 for holding the flexible substrate 1180 in a rolled, stowed configuration against an expandable member according to examples described herein. Fig.11F , the flexible substrate 1180 is substantially similar to the flexible substrates described in the previous embodiments. For example, the flexible substrate 1180 includes a base 1182, which may include an electrically insulating polymer material (such as a polyimide, polyester, or other suitable thermoplastic or thermosetting polymer film). The base 1182 includes a head portion (e.g., a distal portion) 1184, an opposite foot portion (e.g., a proximal portion) 1186, a first peripheral side portion 1188, and a second peripheral side portion 1190. The base 1182 also includes an electrode array 1192 disposed thereon. As described above and Fig.11F As shown in FIG. 1 , the flexible substrate 1180 includes a plurality of adjustment members 1194 extending outwardly from the head portion 1184 and the foot portion 1186. In one example embodiment, the adjustment members 1194 may range in length from about 5-15 mm.

[0163] In one embodiment, the adjustment member 1194 can be heat treated to create a hook shape for the adjustment member 1194 (i.e., the adjustment member 1194 is treated to provide thermal memory of the hook shape). When the flexible substrate 1180 is rolled into its stowed configuration, the hook-shaped adjustment member 1194 is arranged to be arranged in place along the proximal and distal portions of the rolled flexible substrate 1180. In this position, the hook-shaped adjustment member 1194 is arranged in a manner similar to that described above with reference to Fig.11D and Fig.11E The C-shaped bracket described similarly holds the flexible substrate 1180 in the rolled, stowed configuration.

[0164] It should be understood that in other example embodiments, the flexible substrate 1120, 1152, 1180 may have any number of layers, and the alignment members 1122, 1150, 1194 may be arranged to capture any suitable number of layers of the flexible substrate 1120, 1152, 1180. For example, in the illustrated embodiment, the alignment members 1122, 1150, 1194 encapsulate the outermost two layers of the flexible substrate 1120, 1152, 1180. However, in other embodiments, the alignment members 1122, 1150, 1194 may alternatively capture three or more layers of the flexible substrate 1120, 1152, 1180 as desired. Furthermore, in some embodiments, a plurality of alignment members 1122, 1150, and / or 1194 may be provided. The plurality of alignment members 1122 , 1150 , and / or 1194 may be at the same or different circumferential portions of the rolled flexible substrate 1120 , 1152 , 1180 and may capture the same layer or different layers of the flexible substrate 1120 , 1152 , 1180 .

[0165] Fig.13 A catheter 1300 is illustrated having a keyed mating feature designed to facilitate retraction of a flexible substrate 1306 after deployment to assist in removing the catheter 1300 from a treatment site in accordance with an example embodiment. In general, the catheter 1300 can have the same or substantially similar features as any of the catheters 300, 500. Therefore, certain details of the catheter 1300 are not described in further detail below to avoid repetition and / or obscuring the more relevant details of this embodiment. Briefly, reference is made to Fig.13 , catheter 1300 includes an elongated member 1302, an expandable member 1304 coupled thereto, and a flexible substrate 1306 coupled to the expandable member 1304 in a similar manner and with similar functionality as previously described with respect to catheters 300, 500.

[0166] In some embodiments, the flexible substrate 1306 maintains its low-profile stowed configuration against the expandable member 1304 via its internal spring force. However, once the flexible substrate 1306 is expanded, it tends to lose some of its holding force. In some embodiments, after various expansion / retraction cycles, when compressed to the stowed position, the flexible substrate 1306 may not be tightly wound against the expandable member 1304. In addition, in some embodiments, once the fluid pressure is removed after treatment, the expandable member 1304 may not be completely retracted back to its initial state. Therefore, compared to the pre-deployment profile, the catheter 1300 may lose its original low-profile configuration after deployment, which may increase the difficulty of removing the catheter 1300 with minimal complications or no complications. Therefore, the catheter 1300 is designed to have features that help address these problems to facilitate catheter removal.

[0167] refer to Fig.13, the flexible substrate 1306 may include one or more mating features 1308 formed thereon. For example, in one embodiment, the flexible substrate 1306 may include one or more mating features 1308 formed on the extended tail region 1310. The one or more mating features 1308 may include any suitable features that can be operated to engage the corresponding components. In one embodiment, the mating features 1308 may include embossed areas (such as notches or slots) or raised areas (such as columns or ridges) or other suitable elements. The catheter 1300 may also include a sheath 1312 having one or more reciprocal mating features 1314, wherein the corresponding elements are designed to mate with the one or more mating features 1308 on the flexible substrate 1306. In an example operation, after the flexible substrate 1306 is deployed, the sheath 1312 may be advanced toward the flexible substrate 1306 to align the corresponding mating features 1308, 1314 with each other. Once the corresponding features 1308, 1314 on the flexible substrate 1306 and the sheath 1312 are aligned and mated, the flexible substrate 1306 can be pulled proximally and retracted into the sheath 1312. In some embodiments, the sheath 1312 can also be used to apply torque on the flexible substrate 1306 to drive it toward a stowed configuration within the sheath 1312 for retraction after treatment is completed. In embodiments where the catheter 1300 is actuated by a robot-assisted manipulator system, the mating feature 1308 for articulating the flexible substrate 1306 can be part of a drive input of a drive unit at the proximal portion of the catheter 1300. The mating feature 1308 can be operably coupled to a reciprocating drive output of a manipulator assembly to place and maintain the flexible substrate 1306 in a stowed configuration (e.g., by rotating the drive output of the manipulator assembly in a first direction). Optionally, flexible substrate 1306 can be returned to the deployed configuration by expanding expandable member 1304 alone or in combination with rotating the manipulator drive output in the second direction opposite to driving mating feature 1308 in the second direction.

[0168] Fig.14 is a schematic illustration of a segmented flexible substrate 1400 for use with any of the catheter designs described herein, according to an example embodiment. Fig.14, the flexible substrate 1400 can be divided into multiple segments 1402, 1404, 1406, 1408 as shown. In some embodiments, the segments 1402, 1404, 1406, 1408 may include wiring (not shown) to independently power the electrode array (not shown) supported thereon relative to each other. In other embodiments, the segments 1402, 1404, 1406, 1408 may be electrically coupled to each other and work in series as a multi-segment electrode array. In either configuration, the segmented flexible substrate 1400 can provide additional flexibility for the catheter delivered by the endoscope to help navigate through tortuous anatomical structures. In addition, this design can also increase the total area of ​​tissue that can be treated simultaneously, thereby reducing the total treatment time and minimizing the potential tissue damage that may be caused when the catheter is repositioned for subsequent treatment. In some embodiments, the segments 1402, 1404, 1406, 1408 can be wrapped around a single expandable member (not shown) operable to substantially simultaneously expand each segment 1402, 1404, 1406, 1408 against tissue for treatment. In other embodiments, each segment 1402, 1404, 1406, 1408 can alternatively have an independently controllable expandable member for selectively expanding the corresponding segment 1402, 1404, 1406, 1408 as needed.

[0169] Fig.15 is a schematic illustration of a catheter 1500 according to one embodiment. Fig.15 , the catheter 1500 can include an inner elongated member 1502 (e.g., an inner shaft), an outer elongated member 1504 (e.g., an outer shaft), a distal tip 1506, an expandable member 1508, and a flexible substrate 1510 arranged in a similar manner to that previously described. In some embodiments, the inner elongated member 1502 and the outer elongated member 1504 can be made of a single piece of nitinol (nickel titanium) hypotube. The hypotube can be selectively laser cut to obtain unique stiffness, push, tracking, and torque characteristics. The hypotube can help provide stiffness to prevent the kinking problem of the expandable member 1508, especially when the expandable member 1508 is an expandable balloon. In some embodiments, the distal tip 1506 can also be designed as an integral component with the elongated members 1502, 1504, and can have a laser cutting pattern with very small spacing to ensure high flexibility and facilitate insertion and navigation through the patient's anatomical structure.

[0170] In some embodiments, when the catheter 1500 is delivered into the esophagus and advanced toward the treatment site, the flexible substrate 1510 may tend to unfold from the expandable member 1508 due to friction and other forces exerted thereon. Therefore, one approach during delivery is to twist the catheter 1500 counterclockwise (e.g., in a tightening direction) to help avoid potential unfolding of the flexible substrate 1510 and hold the flexible substrate 1510 in place against the expandable member 1508. This approach is not particularly ergonomic and may require twisting the catheter 1500 multiple times and continuously during delivery to counteract the unfolding. Therefore, in some embodiments, the catheter 1500 may also include a spring-based mechanism (not shown) for continuously applying torque to the catheter 1500 in a counterclockwise direction as the catheter 1500 is advanced through the esophagus and reaches the treatment site. In a manual approach, the spring-based mechanism can be activated using a button, lever, or other suitable actuatable device on or in operably connected to the catheter 1500. In some embodiments, the spring-based mechanism can be activated via a semi-robotic or fully robotic system (e.g., Figure 2 The system 100 of the embodiment can be operated to alleviate any ergonomic issues for the operator. In some embodiments, this twisting motion can assist the trackability of the catheter 1500 by reducing the static friction associated therewith.

[0171] Figures 16A-16D Various examples of a flexible substrate and an electrode array coupled to an expandable member for use with a catheter for treating target tissue in a manner similar to that described in the previous example embodiments are collectively illustrated. Figures 16A-16D Certain details of the catheter are further described to avoid duplication and / or obscuring the more relevant details of the illustrated embodiment. It should be understood that the description associated with other catheter embodiments described herein (e.g., catheters 300, 500, 800) can be used in conjunction with reference to the present invention. Figures 16A-16D Additional details are described in conjunction with the General Reference Figures 16A-16D The following description provides various examples of flexible substrate configurations designed to help ensure desired performance of the electrode array and avoid creating unintended current paths between electrodes when the electrode array is deployed and energized for treatment.

[0172] Fig.16A Schematically illustrated is a distal portion of a catheter (not shown) including a flexible substrate 1600 coupled to an expandable member 1602 in a manner similar to that previously described with reference to any of the catheter embodiments described herein. Fig.16A, the flexible substrate 1600 includes an electrode array 1604 disposed along a base 1606 of the flexible substrate 1600. As previously described, the electrode array 1604 can be in any suitable configuration operable to generate an electric field to provide electroporation and / or electrolysis for tissue treatment. For example, the electrode array 1604 can include a plurality of metal traces 1608, 1610, 1612, 1614 deposited on the flexible substrate 1600, wherein the metal traces 1608, 1610, 1612, 1614 include any suitable conductive material, such as gold, copper, stainless steel, titanium, graphene, graphite, etc. For use with electroporation in conjunction with electrolysis, the material of the traces 1608, 1610, 1612, 1614 can be selected so that the electrode material does not actively participate in the electrolysis product and / or does not leave material residue when an electric current is applied. For example, the electrode material can be selected to minimize ion transfer from the electrode material to the target tissue. For example, steel may be less preferred. Titanium and gold may participate in the electrolysis process to some extent, however they may not produce toxic residues and may be used in some examples. In some examples, titanium may be used and may be preferred. In some examples, stainless steel may be used. In some examples, two separate metals may be used, such as zinc and aluminum. In one example arrangement, the traces 1608, 1610, 1612, 1614 are spaced apart from one another along the base 1606 to help ensure the desired current path when the electrode array 1604 is energized. For example, referring to Fig.16A , the traces 1608, 1610, 1612, 1614 are all 1-2 mm wide and can be separated from each other by a spacing of about 3 mm (or between 1-5 mm). The first trace (e.g., trace 1608) closest to the proximal edge portion 1616 of the base 1606 and the last trace (e.g., trace 1614) closest to the distal edge portion 1618 of the base 1606 are both offset from the corresponding edge portion 1616, 1618 by a buffer zone of about 1 mm. In other words, there is a 1 mm spacing between the proximal portion 1616 and the distal portion 1618 of the base 1606 and the location of the corresponding traces 1608, 1614.

[0173] In some examples, small buffer areas along the proximal portion 1616 and / or distal portion 1618 of the base 1606 may result in unintentional exposure of underlying trace segments of the electrode array 1604 (e.g., trace segments in a layer below the outermost portion of the wrapped flexible substrate 1600) during expansion of the expandable member 1602 and / or during positioning of the catheter for treatment. Unintentional exposure of underlying trace segments may result in inaccurate energy delivery during treatment, noise in impedance measurements, creation of unintended current paths between traces of the electrode array 1604, and / or other undesirable performance behaviors or characteristics of the flexible substrate 1600. For example, Fig. 16BAn example of a flexible substrate 1600 in a partially displaced position after expansion of an expandable member 1602 is illustrated.

[0174] refer to Fig. 16B In some examples, the layers of flexible substrate 1600 may be unintentionally displaced as described above. Fig. 16B , the flexible substrate 1600 is illustrated as being in a displaced position, wherein both the proximal portion 1616 and the distal portion 1618 of the flexible substrate 1600 are displaced relative to an original position of the flexible substrate 1600 (eg, Fig.16A 1600 is displaced or offset proximally. This proximal displacement of the flexible substrate 1600 exposes and exposes the underlying trace segments 1620 of the electrode array 1604 adjacent to the traces 1614. Fig. 16B As shown, the exposed trace segment 1620 is adjacent to the trace 1614 and, when the electrode array 1604 is energized, the normal current path between the adjacent traces 1612, 1614 is disrupted (as shown by path A), and an unintended current path is created between the traces 1612, 1614 and the exposed trace segment 1620 (as shown by path B). To help minimize the effects of positional shifts of the flexible substrate 1600, additional cushioning areas along the proximal portion 1616 and / or distal portion 1618 of the base 1606 can be incorporated into the design of the flexible substrate 1600, as described further below.

[0175] Fig. 16C An example embodiment of a flexible substrate 1650 having a base 1652 with an extended proximal cushioning region 1654 and an extended distal cushioning region 1656 is illustrated. The proximal cushioning region 1654 is disposed between a proximal portion 1658 of the base 1652 and a first trace 1660, and the distal cushioning region 1656 is positioned between a distal portion 1662 and a second trace 1664. Fig. 16C , the additional buffer regions 1654, 1656 help ensure that the trace segments in the lower winding portion of the flexible substrate 1650 (e.g., Fig. 16B In other words, the buffer regions 1654, 1656 of the base 1652 help ensure that the underlying trace segments remain covered when the flexible substrate 1650 is displaced to avoid unintentional interactions between the trace segments, such as reference Fig. 16B In some embodiments, the buffer regions 1654, 1656 can each be in the range of between 3 mm and 7 mm to provide wide coverage for any displacement of the flexible substrate 1650. In some embodiments, the buffer region can be greater than or equal to the spacing between adjacent traces of the electrode array.

[0176] In some embodiments (such as Fig. 16C In some embodiments, the cushioning area can be symmetrical (e.g., having the same width) along the proximal and distal portions of the flexible substrate. In other embodiments, the flexible substrate can have a larger cushioning area along the distal portion than the proximal portion (or vice versa). For example, Fig.16D An example of a flexible substrate 1680 with an asymmetric cushioning design is illustrated, which includes a shorter cushioning area 1682 along a proximal portion 1684 and a larger cushioning area 1686 along a distal portion 1688. In some embodiments, during catheter delivery, the flexible substrate 1680 may tend to shift proximally. For example, in some cases, the catheter can be advanced (e.g., moved forward in a proximal to distal direction) from a first treatment area to a second treatment area. When the catheter is advanced, the corresponding reaction force applied to the flexible substrate 1680 pushes the outermost layer of the flexible substrate 1680 proximally (e.g., opposite to the direction of catheter advancement), thereby resulting in potential exposure of the lower trace segment along the distal portion 1688. Therefore, since exposure along the distal portion 1688 of the flexible substrate 1680 is more likely than exposure along the proximal portion 1684 when the catheter is advanced, a larger distal cushioning area 1686 is advantageous.

[0177] In addition, in some embodiments, it may also be beneficial to have a shorter proximal buffer region 1682 on the proximal portion 1684 of the flexible substrate 1680. In some examples, an endoscope (or other medical device) may follow behind a catheter during delivery to visualize within a tissue lumen. In these examples, a larger proximal buffer region 1682 along the proximal portion 1684 of the flexible substrate 1680 may obstruct visibility of the traces of the electrode array (e.g., traces 1690) from an endoscope because the flexible substrate 1680 is opaque. Therefore, having a shorter proximal buffer region 1682 can help improve visibility of the electrode array on the flexible substrate 1680, while a larger distal buffer region 1686 helps minimize potential exposure of the underlying trace segments as described above.

[0178] In other examples, the flexible substrate (not shown) may have Fig.16D The flexible substrate 1680 of the embodiment of the present invention is an inverse configuration of the flexible substrate 1680, wherein the flexible substrate includes a larger cushioning area along the proximal portion and a shorter cushioning area along the distal portion. This configuration can help minimize exposure of underlying traces along the proximal portion of the flexible substrate, such as may occur when the catheter is moved proximally (e.g., in contrast to the reference Fig. 16CIn some cases, the catheter may be retracted (e.g., moved backward in a distal-to-proximal direction) from a first treatment region to a second treatment region. When the catheter is retracted, a corresponding reaction force exerted on the flexible substrate pushes the outermost layer of the flexible substrate distally, thereby causing potential exposure of the underlying trace segments along the proximal portion. Therefore, in these cases, a larger buffer area on the proximal portion is beneficial.

[0179] It should be understood that the design of the catheter delivery system provided herein and the example embodiments of potential clinical applications associated therewith are not limiting. There are many other configurations of delivery systems and applications that will benefit from using the disclosed subject matter. In addition, it should be understood that any of the above-mentioned embodiments or processes or specific features associated therewith can be combined with one or more other embodiments and / or processes, or separated and / or performed between separate devices or device parts, according to the present systems, devices and methods.

[0180] Finally, the present disclosure is intended only to illustrate the present apparatus, devices, systems and methods and should not be interpreted as limiting the appended claims to any particular embodiment or group of embodiments. Therefore, although the present disclosure has been described in particular detail with reference to the exemplary embodiments, it should also be understood that many modifications and alternative embodiments may be practiced without departing from the broader and intended spirit and scope of the present disclosure as set forth in the appended claims. Therefore, the description and drawings are to be regarded as illustrative and are not intended to limit the scope of the appended claims.

[0181] In addition, the present disclosure also includes the following embodiments:

[0182] Embodiment 1. A system for tissue treatment, the system comprising:

[0183] a flexible substrate having a head portion and a foot portion and a first peripheral side portion and a second peripheral side portion each spanning between the head portion and the foot portion, the flexible substrate including a first arm segment extending outwardly from the head portion and a second arm segment extending outwardly from the foot portion; and

[0184] An electrode array is disposed on the flexible substrate, wherein at least a portion of the electrode array extends to one of the first arm segment or the second arm segment.

[0185] Embodiment 2. The system of Embodiment 1, wherein the first arm segment and the second arm segment are aligned relative to each other along a first axis, the first axis extending across the flexible substrate from the head portion to the foot portion.

[0186] Embodiment 3. The system of Embodiment 1, wherein the first arm segment and the second arm segment are aligned relative to each other along one of the first peripheral side portion or the second peripheral side portion of the flexible substrate.

[0187] Embodiment 4. The system of Embodiment 1, wherein the first arm segment is substantially orthogonal to the head portion and the second arm segment is substantially orthogonal to the foot portion.

[0188] Embodiment 5. The system of Embodiment 1, wherein the other of the first arm segment or the second arm segment lacks the electrode array.

[0189] Embodiment 6. The system of Embodiment 1, wherein the first arm segment and the second arm segment are each formed as an integral part of the flexible substrate.

[0190] Embodiment 7. The system of Embodiment 1, further comprising one or more holes formed on the flexible substrate, wherein the one or more holes are disposed between portions of the electrode array.

[0191] Embodiment 8. A system according to embodiment 7, wherein the electrode array includes a first trace element and a second trace element offset from each other on the flexible substrate, and wherein at least some of the one or more holes are arranged on the flexible substrate between the first trace element and the second trace element.

[0192] Embodiment 9. According to the system of embodiment 1, the flexible substrate also includes a top surface and an opposite bottom surface, wherein the first peripheral side portion of the flexible substrate includes a first edge surface spanning from the top surface to the bottom surface, and wherein the second peripheral side portion of the flexible substrate includes a second edge surface spanning from the top surface to the bottom surface, and the system also includes a protective coating covering at least one of the first edge surface or the second edge surface of the flexible substrate.

[0193] Embodiment 10 The system of Embodiment 9, wherein a length of the first perimeter side portion of the flexible substrate is different than a length of the second perimeter side portion of the flexible substrate.

[0194] Embodiment 11. The system of Embodiment 10, wherein a length of the first perimeter side portion of the flexible substrate is greater than a length of the second perimeter side portion of the flexible substrate.

[0195] Embodiment 12 The system of Embodiment 10, wherein a length of the first perimeter side portion of the flexible substrate is less than a length of the second perimeter side portion of the flexible substrate.

[0196] Embodiment 13. The system of Embodiment 9, wherein the electrode array is disposed on the top surface of the flexible substrate, and wherein the protective coating covers at least a portion of the electrode array.

[0197] Embodiment 14. The system of Embodiment 1, wherein the flexible substrate further comprises a top surface and an opposing bottom surface, the system further comprising a protective coating covering at least a portion of the top surface of the flexible substrate.

[0198] Embodiment 15. The system of Embodiment 14, wherein the protective coating covers an outer edge surface of the flexible substrate.

[0199] Embodiment 16. A system according to embodiment 1, wherein the electrode array comprises a plurality of spaced-apart traces, wherein a first trace is closest to a proximal end of the flexible substrate and a second trace is closest to a distal end of the flexible substrate, and wherein the flexible substrate comprises a buffer region without electrode traces, wherein the buffer region is between at least one of: a) the distance between the first trace and the proximal end of the flexible substrate; or b) the distance between the second trace and the distal end of the flexible substrate.

[0200] Embodiment 17. The system of Embodiment 16, wherein the buffer region is between a) a distance between the first trace and the proximal end of the flexible substrate and b) a distance between the second trace and the distal end of the flexible substrate.

[0201] Embodiment 18. The system of Embodiment 17, wherein a length of the buffer region between the first trace and the proximal end of the flexible substrate is greater than a length of the buffer region between the second trace and the distal end of the flexible substrate.

[0202] Embodiment 19. The system of Embodiment 17, wherein a length of the buffer region between the first trace and the proximal end of the flexible substrate is less than a length of the buffer region between the second trace and the distal end of the flexible substrate.

[0203] Embodiment 20. A system according to any one of embodiments 16-19, wherein the length of the buffer region is in the range of between 3 mm and 7 mm.

[0204] Embodiment 21. A system according to any of Embodiments 16-19, wherein the length of the buffer region is equal to or greater than the spacing between adjacent traces of the electrode array.

[0205] Embodiment 22. A system for tissue treatment, the system comprising:

[0206] Slender member;

[0207] an expandable member coupled to the elongated member, wherein the expandable member is radially expandable relative to the elongated member; and

[0208] A flexible substrate comprising an electrode array disposed thereon, the flexible substrate having a head portion and a foot portion and a first peripheral side portion and a second peripheral side portion both spanning between the head portion and the foot portion, the flexible substrate comprising a first arm segment extending outwardly from the head portion and a second arm segment extending outwardly from the foot portion, wherein when in a stowed position, the flexible substrate surrounds at least a portion of the expandable member, wherein one of the first arm segment or the second arm segment of the flexible substrate is coupled to the expandable member to hold the flexible substrate against the expandable member in the stowed position, and wherein the flexible substrate is capable of expanding from the stowed position to a deployed position in response to radial expansion of the expandable member.

[0209] Embodiment 23. The system of Embodiment 22, wherein when the flexible substrate is in the deployed position, the one of the first arm segment or the second arm segment is coupled to the expandable member.

[0210] Example 24. The system of Example 22, wherein the expandable member is coupled to a distal portion of the elongated member.

[0211] Example 25. A system as described in Example 22, wherein at least a portion of the slender member extends distally of the expandable member.

[0212] Example 26. The system of Example 22 further comprises one or more wires coupled to the electrode array and configured to supply power to the electrode array, wherein the one or more wires hold the flexible substrate in place along a proximal portion of the elongated member.

[0213] Example 27. A system as described in Example 22, wherein the slender member includes a distal portion and a proximal portion, and wherein the expandable member is coupled to the slender member between the distal portion and the proximal portion.

[0214] Embodiment 28. A system according to Embodiment 27, wherein one of the first arm segment or the second arm segment of the flexible substrate is coupled to the expandable member near the distal portion of the slender member to hold the flexible substrate against the expandable member.

[0215] Example 29. A system according to Example 28, wherein the other of the first arm segment or the second arm segment of the flexible substrate is coupled to one or more wires configured to power the electrode array, and the one or more wires hold the flexible substrate against the expandable member near the proximal portion of the slender member.

[0216] Example 30. According to the system of Example 22, the flexible substrate also includes a front edge defined along one of the head portion or the foot portion of the flexible substrate, the front edge corresponding to the first arm segment or the second arm segment that couples the flexible substrate to the expandable member when the flexible substrate is in the stowed position, and the system also includes a first pad adjacent to the front edge of the flexible substrate for preventing tissue trauma during system delivery.

[0217] Embodiment 31. The system of Embodiment 30, wherein the first pad contacts the leading edge of the flexible substrate.

[0218] Embodiment 32. A system according to embodiment 30, wherein the flexible substrate further includes a rear edge defined along the other of the head portion or the foot portion of the flexible substrate, and the system further includes a second pad adjacent to the rear edge of the flexible substrate to prevent tissue trauma during removal of the system.

[0219] Embodiment 33. The system of Embodiment 32, wherein the second pad contacts the rear edge of the flexible substrate.

[0220] Example 34. According to the system of Example 32, the flexible substrate also includes a front edge defined along one of the head portion or the foot portion of the flexible substrate, the front edge corresponding to the first arm segment or the second arm segment that couples the flexible substrate to the expandable member when the flexible substrate is in the stowed position, wherein the expandable member is partially expanded to form a first pad adjacent to the front edge of the flexible substrate to prevent tissue trauma during system delivery.

[0221] Embodiment 35. The system of Embodiment 34, wherein the first pad contacts the leading edge of the flexible substrate.

[0222] Example 36. According to the system of Example 34, the flexible substrate also includes a rear edge defined along the other of the head portion or the foot portion of the flexible substrate, wherein the expandable member is partially expanded to form a second pad adjacent to the rear edge of the flexible substrate to prevent tissue trauma during system removal.

[0223] Embodiment 37. The system of Embodiment 36, wherein the second pad contacts the rear edge of the flexible substrate.

[0224] Embodiment 38. The system of Embodiment 22, wherein the first arm segment and the second arm segment are aligned relative to each other along a first axis, the first axis extending across the flexible substrate from the head portion to the foot portion.

[0225] Embodiment 39 The system of Embodiment 22, wherein the first arm segment and the second arm segment are aligned relative to each other along one of the first peripheral side portion or the second peripheral side portion of the flexible substrate.

[0226] Embodiment 40. The system of Embodiment 22, wherein the first arm segment is substantially orthogonal to the head portion and the second arm segment is substantially orthogonal to the foot portion.

[0227] Embodiment 41. A system according to Embodiment 22, wherein the other of the first arm segment or the second arm segment lacks the electrode array.

[0228] Embodiment 42. The system of Embodiment 22, wherein the first arm segment and the second arm segment are each formed as an integral part of the flexible substrate.

[0229] Embodiment 43. The system of Embodiment 22 further comprising one or more holes formed on the flexible substrate, wherein the one or more holes are disposed between portions of the electrode array.

[0230] Embodiment 44. A system according to Embodiment 43, wherein the electrode array includes a first trace element and a second trace element offset from each other on the flexible substrate, and wherein at least some of the one or more holes are arranged on the flexible substrate between the first trace element and the second trace element.

[0231] Embodiment 45. A system according to embodiment 22, wherein the flexible substrate further includes a top surface and an opposite bottom surface, wherein the first peripheral side portion of the flexible substrate includes a first edge surface spanning from the top surface to the bottom surface, and wherein the second peripheral side portion of the flexible substrate includes a second edge surface spanning from the top surface to the bottom surface, and the system further includes a protective coating covering at least one of the first edge surface or the second edge surface of the flexible substrate.

[0232] Embodiment 46 The system of Embodiment 45, wherein a length of the first perimeter side portion of the flexible substrate is different than a length of the second perimeter side portion of the flexible substrate.

[0233] Embodiment 47 The system of Embodiment 46, wherein a length of the first perimeter side portion of the flexible substrate is greater than a length of the second perimeter side portion of the flexible substrate.

[0234] Embodiment 48 The system of Embodiment 46, wherein a length of the first perimeter side portion of the flexible substrate is less than a length of the second perimeter side portion of the flexible substrate.

[0235] Embodiment 49. The system of Embodiment 45, wherein the electrode array is disposed on the top surface of the flexible substrate, and wherein the protective coating covers at least a portion of the electrode array.

[0236] Embodiment 50. The system of Embodiment 22, wherein the flexible substrate further comprises a top surface and an opposing bottom surface, the system further comprising a protective coating covering at least a portion of the top surface of the flexible substrate.

[0237] Embodiment 51. The system of Embodiment 50, wherein the protective coating covers an outer edge surface of the flexible substrate.

[0238] Embodiment 52. A system according to embodiment 22, wherein the electrode array comprises a plurality of spaced-apart traces, wherein a first trace is closest to a proximal end of the flexible substrate and a second trace is closest to a distal end of the flexible substrate, and wherein the flexible substrate comprises a buffer region without electrode traces, the buffer region being between at least one of: a) the distance between the first trace and the proximal end of the flexible substrate; or b) the distance between the second trace and the distal end of the flexible substrate.

[0239] Embodiment 53. The system of Embodiment 52, wherein the buffer region is between a) a distance between the first trace and the proximal end of the flexible substrate and b) a distance between the second trace and the distal end of the flexible substrate.

[0240] Embodiment 54. The system of Embodiment 53, wherein a length of the buffer region between the first trace and the proximal end of the flexible substrate is greater than a length of the buffer region between the second trace and the distal end of the flexible substrate.

[0241] Embodiment 55. The system of Embodiment 53, wherein a length of the buffer region between the first trace and the proximal end of the flexible substrate is less than a length of the buffer region between the second trace and the distal end of the flexible substrate.

[0242] Example 56. A system according to any of Examples 52-55, wherein the length of the buffer region is in the range of between 3 mm and 7 mm.

[0243] Embodiment 57. A system according to any of Embodiments 52-55, wherein the length of the buffer region is equal to or greater than the spacing between adjacent traces of the electrode array.

[0244] Embodiment 58. A system for tissue treatment, the system comprising:

[0245] Slender member;

[0246] an expandable member coupled to the elongated member, wherein the expandable member is radially expandable relative to the elongated member;

[0247] a flexible substrate including an electrode array disposed thereon, wherein the flexible substrate is movable from a stowed position in which the flexible substrate surrounds at least a portion of the expandable member and has a first outer diameter to a deployed position in which the flexible substrate expands to a second outer diameter greater than the first outer diameter in response to radial expansion of the expandable member; and

[0248] An adjustment member is coupled to at least one of the flexible substrate or the expandable member, wherein the adjustment member is adjustable to retain the flexible substrate in the stowed position.

[0249] Embodiment 59. The system of Embodiment 58, wherein the adjustment member is further adjustable to control movement of the flexible substrate from the stowed position to the deployed position after an initial adjustment to maintain the flexible substrate in the stowed position.

[0250] Embodiment 60 The system of Embodiment 58, wherein the adjustment member is further adjustable to drive the flexible substrate from the deployed position to the stowed position.

[0251] Embodiment 61. The system of Embodiment 58, wherein the flexible substrate further comprises one or more holes formed thereon, and wherein the adjustment member is coupled to the flexible substrate through at least some of the one or more holes.

[0252] Embodiment 62. A system according to Embodiment 61, wherein the adjustment member is a cable or wire, and the cable or wire is woven through at least some of the one or more holes formed on the flexible substrate to couple the adjustment member to the flexible substrate.

[0253] Embodiment 63. The system of Embodiment 58, wherein the adjustment member is releasable from the flexible substrate to facilitate movement of the flexible substrate from the stowed position to the deployed position.

[0254] Embodiment 64 The system of Embodiment 58, wherein the adjustment member limits expansion of the flexible substrate in the deployed position to a predetermined outer diameter.

[0255] Embodiment 65. A system according to Embodiment 64, wherein the flexible substrate further includes one or more holes formed thereon, and wherein the adjustment member is coupled to the flexible substrate through at least some of the one or more holes, and the adjustment member contacts the flexible substrate to limit the expansion to the predetermined outer diameter.

[0256] Embodiment 66. The system of Embodiment 58, wherein the flexible substrate is coupled to the expandable member, wherein the adjustment member is coupled to the expandable member, and wherein the adjustment member adjusts the expandable member to maintain the flexible substrate in the stowed position.

[0257] Example 67. The system of Example 58, wherein the expandable member is coupled to a distal portion of the elongated member.

[0258] Example 68. The system of Example 58, wherein at least a portion of the elongated member extends distally of the expandable member.

[0259] Embodiment 69. The system of Embodiment 58, wherein the adjustment member comprises a tensioning element, and wherein the tensioning element adjusts the flexible substrate in response to tension applied to the tensioning element to maintain the flexible substrate in the stowed position.

[0260] Embodiment 70. The system of Embodiment 69, wherein the tensioning element is a cable or a wire.

[0261] Embodiment 71. The system of Embodiment 58, wherein the adjustment member comprises a tensioning element, and wherein tension in the tensioning element is releasable to facilitate adjustment of the flexible substrate from the stowed position to the deployed position.

[0262] Embodiment 72. The system of Embodiment 58, wherein the adjustment member comprises a tensioning element, and wherein tension in the tensioning element can be released by cutting the tensioning element to facilitate adjustment of the flexible substrate from the stowed position to the deployed position.

[0263] Embodiment 73. The system of Embodiment 58, wherein the adjustment member comprises a tensioning element, and wherein the tensioning element drives the flexible substrate from the deployed position to the stowed position in response to tension applied to the tensioning element.

[0264] Embodiment 74. The system of Embodiment 58, wherein the adjustment member comprises a tensioning element, and wherein the tensioning element is releasable from the flexible substrate to facilitate movement of the flexible substrate from the stowed position to the deployed position.

[0265] Embodiment 75. A system according to Embodiment 58, wherein the flexible substrate further includes one or more holes formed thereon, and wherein the adjustment member is a tensioning element coupled to the flexible substrate through at least some of the one or more holes.

[0266] Embodiment 76. A system according to Embodiment 75, wherein the tensioning element is a cable or wire that is woven through at least some of the one or more holes formed on the flexible substrate to couple the tensioning element to the flexible substrate.

[0267] Embodiment 77. A system according to embodiment 58, wherein the flexible substrate further includes one or more holes formed thereon, and wherein the adjustment member is a tensioning element coupled to the flexible substrate through at least some of the one or more holes, the tensioning element contacting the flexible substrate to limit the expansion to a predetermined outer diameter.

[0268] Embodiment 78. A system according to embodiment 58, wherein the flexible substrate further includes a top surface and an opposite bottom surface, wherein a first peripheral side portion of the flexible substrate includes a first edge surface spanning from the top surface to the bottom surface, and wherein a second peripheral side portion of the flexible substrate includes a second edge surface spanning from the top surface to the bottom surface, and wherein the system further includes a protective coating covering at least one of the first edge surface or the second edge surface of the flexible substrate.

[0269] Embodiment 79 The system of Embodiment 78, wherein a length of the first perimeter side portion of the flexible substrate is different than a length of the second perimeter side portion of the flexible substrate.

[0270] Embodiment 80 The system of Embodiment 79, wherein a length of the first perimeter side portion of the flexible substrate is greater than a length of the second perimeter side portion of the flexible substrate.

[0271] Embodiment 81 The system of Embodiment 79, wherein a length of the first perimeter side portion of the flexible substrate is less than a length of the second perimeter side portion of the flexible substrate.

[0272] Embodiment 82. The system of Embodiment 78, wherein the electrode array is disposed on the top surface of the flexible substrate, and wherein the protective coating covers at least a portion of the electrode array.

[0273] Embodiment 83. The system of Embodiment 58, wherein the flexible substrate further comprises a top surface and an opposite bottom surface, the system further comprising a protective coating covering at least a portion of the top surface of the flexible substrate.

[0274] Embodiment 84. The system of Embodiment 83, wherein the protective coating covers an outer edge surface of the flexible substrate.

[0275] Embodiment 85. A system according to embodiment 58, wherein the electrode array comprises a plurality of spaced-apart traces, wherein a first trace is closest to a proximal end of the flexible substrate and a second trace is closest to a distal end of the flexible substrate, and wherein the flexible substrate comprises a buffer region without electrode traces, the buffer region being between at least one of: a) the distance between the first trace and the proximal end of the flexible substrate; or b) the distance between the second trace and the distal end of the flexible substrate.

[0276] Embodiment 86 The system of Embodiment 85, wherein the buffer region is between a) a distance between the first trace and the proximal end of the flexible substrate and b) a distance between the second trace and the distal end of the flexible substrate.

[0277] Embodiment 87 The system of Embodiment 86, wherein a length of the buffer region between the first trace and the proximal end of the flexible substrate is greater than a length of the buffer region between the second trace and the distal end of the flexible substrate.

[0278] Embodiment 88 The system of Embodiment 86, wherein a length of the buffer region between the first trace and the proximal end of the flexible substrate is less than a length of the buffer region between the second trace and the distal end of the flexible substrate.

[0279] Embodiment 89. A system according to any of embodiments 85-88, wherein the length of the buffer region is in the range of between 3 mm and 7 mm.

[0280] Embodiment 90. A system according to any of Embodiments 84-87, wherein the length of the buffer region is equal to or greater than the spacing between adjacent traces of the electrode array.

[0281] Embodiment 91. A system for tissue treatment, the system comprising:

[0282] a flexible substrate having a proximal end and a distal end and a first peripheral side portion and a second peripheral side portion each spanning between the proximal end and the distal end; and

[0283] an electrode array disposed on the flexible substrate, wherein the electrode array comprises a plurality of spaced-apart traces, wherein a first trace is closest to the proximal end of the flexible substrate and a second trace is closest to the distal end of the flexible substrate,

[0284] The flexible substrate includes a buffer region without electrode traces, the buffer region being disposed between at least one of: a) a distance between the first trace and the proximal end of the flexible substrate; or b) a distance between the second trace and the distal end of the flexible substrate, and wherein a length of the buffer region is equal to or greater than a spacing between adjacent traces of the electrode array.

[0285] Embodiment 92. The system of Embodiment 91, wherein the buffer region is between a) a distance between the first trace and the proximal end of the flexible substrate and b) a distance between the second trace and the distal end of the flexible substrate.

[0286] Embodiment 93. The system of Embodiment 92, wherein a length of the buffer region between the first trace and the proximal end of the flexible substrate is greater than a length of the buffer region between the second trace and the distal end of the flexible substrate.

[0287] Embodiment 94. The system of Embodiment 92, wherein a length of the buffer region between the first trace and the proximal end of the flexible substrate is less than a length of the buffer region between the second trace and the distal end of the flexible substrate.

[0288] Example 95. A system according to any of Examples 91-94, wherein the length of the buffer region is in the range of between 3 mm and 7 mm.

[0289] Embodiment 96. According to the system of embodiment 91, the flexible substrate also includes a top surface and an opposite bottom surface, wherein the first peripheral side portion of the flexible substrate includes a first edge surface spanning from the top surface to the bottom surface, and wherein the second peripheral side portion of the flexible substrate includes a second edge surface spanning from the top surface to the bottom surface, and the system also includes a protective coating covering at least one of the first edge surface or the second edge surface of the flexible substrate.

[0290] Embodiment 97 The system of Embodiment 96, wherein a length of the first perimeter side portion of the flexible substrate is different than a length of the second perimeter side portion of the flexible substrate.

[0291] Embodiment 98 The system of Embodiment 97, wherein a length of the first perimeter side portion of the flexible substrate is greater than a length of the second perimeter side portion of the flexible substrate.

[0292] Embodiment 99. The system of Embodiment 97, wherein a length of the first perimeter side portion of the flexible substrate is less than a length of the second perimeter side portion of the flexible substrate.

[0293] Embodiment 100. The system of Embodiment 96, wherein the electrode array is disposed on the top surface of the flexible substrate, and wherein the protective coating covers at least a portion of the electrode array.

[0294] Embodiment 101. The system of Embodiment 91, wherein the flexible substrate further comprises a top surface and an opposite bottom surface, the system further comprising a protective coating covering at least a portion of the top surface of the flexible substrate.

[0295] Embodiment 102. The system of Embodiment 101, wherein the protective coating covers an outer edge surface of the flexible substrate.

Claims

1. A system for tissue treatment, the system comprising: a flexible substrate having a head portion and a foot portion and a first peripheral side portion and a second peripheral side portion each spanning between the head portion and the foot portion, the flexible substrate comprising a first arm segment extending outwardly from the head portion and a second arm segment extending outwardly from the foot portion; as well as An electrode array is disposed on the flexible substrate, wherein at least a portion of the electrode array extends to one of the first arm segment or the second arm segment. 2 . The system of claim 1 , wherein the first arm segment and the second arm segment are aligned relative to each other along a first axis, the first axis extending across the flexible substrate from the head portion to the foot portion. 3 . The system of claim 1 , wherein the first arm segment and the second arm segment are aligned relative to each other along one of the first peripheral side portion or the second peripheral side portion of the flexible substrate.

4. The system of claim 1, wherein the first arm segment is substantially orthogonal to the head portion and the second arm segment is substantially orthogonal to the foot portion.

5. The system of claim 1, wherein the other of the first arm segment or the second arm segment is devoid of the electrode array.

6. The system of claim 1, wherein the first arm segment and the second arm segment are each formed as an integral part of the flexible substrate.

7. The system of claim 1, further comprising one or more holes formed in the flexible substrate, wherein the one or more holes are disposed between portions of the electrode array.

8. A system according to claim 7, wherein the electrode array includes a first trace element and a second trace element offset from each other on the flexible substrate, and wherein at least some of the one or more holes are arranged on the flexible substrate between the first trace element and the second trace element.

9. The system of claim 1 , wherein the flexible substrate further comprises a top surface and an opposite bottom surface, wherein the first peripheral side portion of the flexible substrate comprises a first edge surface spanning from the top surface to the bottom surface, and wherein the second peripheral side portion of the flexible substrate comprises a second edge surface spanning from the top surface to the bottom surface, the system further comprising a protective coating covering at least one of the first edge surface or the second edge surface of the flexible substrate.

10. The system of claim 9, wherein a length of the first perimeter side portion of the flexible substrate is different than a length of the second perimeter side portion of the flexible substrate.

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